Category Archives: Pennsylvania Stem Cells

Basel, August 30, 2017 - Novartis announced today that the US Food and Drug Administration (FDA) has approved Kymriah(TM)(tisagenlecleucel) suspension for intravenous infusion, formerly CTL019, the first chimeric antigen receptor T cell (CAR-T) therapy, for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. Kymriah is a novel immunocellular therapy and a one-time treatment that uses a patient's own T cells to fight cancer. Kymriah is the first therapy based on gene transfer approved by the FDA.

"At Novartis, we have a long history of being at the forefront of transformative cancer treatment," said Joseph Jimenez, CEO of Novartis. "Five years ago, we began collaborating with the University of Pennsylvania and invested in further developing and bringing what we believed would be a paradigm-changing immunocellular therapy to cancer patients in dire need. With the approval of Kymriah, we are once again delivering on our commitment to change the course of cancer care."

"We are so proud to be part of this historic moment in cancer treatment and are deeply grateful to our researchers, collaborators, and the patients and families who participated in the Kymriah clinical program," said Bruno Strigini, CEO of Novartis Oncology. "As a breakthrough immunocellular therapy for children and young adults who desperately need new options, Kymriah truly embodies our mission to discover new ways to improve patient outcomes and the way cancer is treated."

The FDA has approved a Risk Evaluation and Mitigation Strategy (REMS) for Kymriah. The REMS program serves to inform and educate healthcare professionals about the risks that may be associated with Kymriah treatment. To support safe patient access, Novartis is establishing a network of certified treatment centers throughout the country which will be fully trained on the use of Kymriah and appropriate patient care.

There has been an urgent need for novel treatment options that improve outcomes for patients with relapsed or refractory (r/r) B-cell precursor ALL, whose prognosis is poor. Patients often undergo multiple treatments including chemotherapy, radiation, targeted therapy or stem cell transplant, yet less than 10% of patients survive five years [2], [3].

Kymriah is an innovative immunocellular therapy that is a one-time treatment. Kymriah uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular expansion and persistence. In 2012, Novartis and the University of Pennsylvania (Penn) entered into a global collaboration to further research, develop and commercialize CAR-T cell therapies, including Kymriah, for the investigational treatment of cancers.

"This therapy is a significant step forward in individualized cancer treatment that may have a tremendous impact on patients' lives," said Carl June, MD, the Richard W. Vague Professor of Immunotherapy, Director of the Center for Cellular Immunotherapies in Penn's Perelman School of Medicine, who is a pioneer of this new treatment. "Through our collaboration with Novartis, we are creating the next wave of immunocellular cancer treatments, and are eager to progress CAR-T therapy in a host of hematologic and other cancer types."

In close collaboration with Novartis and Penn, Children's Hospital of Philadelphia (CHOP) was the first institution to investigate Kymriah in the treatment of pediatric patients leading the single site trial.

"Tisagenlecleucel is the first CAR-T therapy to demonstrate early, deep and durable remission in children and young adults with relapsed or refractory B-cell ALL," said Stephan Grupp, MD, PhD, the Yetta Deitch Novotny Professor of Pediatrics at the Perelman School of Medicine at Penn, and Director of the Cancer Immunotherapy Frontier Program at Children's Hospital of Philadelphia (CHOP). "We've never seen anything like this before and I believe this therapy may become the new standard of care for this patient population."

Novartis is committed to ensuring eligible patients have access to Kymriah, and is working to ensure payers understand the value of Kymriah and provide coverage for patients. To address the unique aspects of the therapy, Novartis has also developed various patient access programs to support safe and timely access for patients. Novartis is also providing traditional support to patients by helping them navigate insurance coverage and providing financial assistance for those who are uninsured or underinsured.

Novartis plans additional filings for Kymriah in the US and EU later this year, including applications with the FDA and European Medicines Agency (EMA), for the treatment of adult patients with r/r diffuse large B-cell lymphoma (DLBCL). Additional filings beyond the US and EU are anticipated in 2018.

Groundbreaking Collaboration with the Centers for Medicare and Medicaid Services Novartis also announced a novel collaboration with the United States Centers for Medicare and Medicaid Services (CMS) focused on improving efficiencies in current regulatory requirements in order to deliver value-based care and ensure access for this specific patient population.

This approach is intended to include indication-based pricing for medicines and supports payments for a medicine, such as Kymriah for its initial indication, based on the clinical outcomes achieved, which would eliminate inefficiencies from the healthcare system. Other value-based approaches related to future indications for Kymriah and CAR-T cell therapies are under discussion.

Furthermore, Novartis is collaborating with CMS to make an outcomes-based approach available to allow for payment only when pediatric and young adult ALL patients respond to Kymriah by the end of the first month. Future potential indications would be reviewed for the most relevant outcomes-based approach.

"Novartis has been at the forefront of outcomes-based pricing and is very pleased to work with CMS on this first-of-its-kind collaboration with a technology that has the potential to transform cancer care," said Joseph Jimenez, CEO of Novartis."We look forward to continuing to work with CMS to potentially expand this approach to other products and disease states."

About Kymriah ManufacturingKymriah will be manufactured for each individual patient using their own cells at the Novartis Morris Plains, New Jersey facility. Novartis has designed a reliable and integrated manufacturing and supply chain platform that allows for an individualized treatment approach on a global scale. This process includes cryopreservation of a patient's harvested (or leukapheresed) cells, giving treating physicians and centers the flexibility to initiate therapy with Kymriah based on the individual patient's condition. Building on our experience, having manufactured CAR-T cells for over 250 patients from 11 countries across various indications, we have demonstrated a reproducible product. Novartis continues to advance its CAR-T manufacturing expertise in Morris Plains, where we have been supplying CAR-T cells for global clinical trials and where we continue to invest in support of the anticipated demand to meet the needs of patients.

Kymriah Pivotal Study ResultsThe FDA approval of Kymriah is based on the results of the pivotal open-label, multicenter, single-arm Phase II ELIANA trial, the first pediatric global CAR-T cell therapy registration trial examining patients in 25 centers in the US, EU, Canada, Australia and Japan. In this Novartis-sponsored study, 68 patients were infused and 63 were evaluable for efficacy. Results show 83% (52 of 63; 95% confidence interval [CI]: 71%-91%) of patients who received treatment with Kymriah achieved complete remission (CR) or CR with incomplete blood count recovery (CRi) within three months of infusion. In addition, no minimal residual disease (MRD) - a blood marker that indicates potential relapse - was detected among responding patients. Median duration of remission was not reached (95% CI: 7.5-NE) [1].

The most common (>20%) adverse reactions in the ELIANA trial are cytokine release syndrome (CRS), hypogammaglobulinemia, infections-pathogen unspecified, pyrexia, decreased appetite, headache, encephalopathy, hypotension, bleeding episodes, tachycardia, nausea, diarrhea, vomiting, viral infectious disorders, hypoxia, fatigue, acute kidney injury and delirium. In the study, 49% of patients treated with Kymriah experienced grade 3 or 4 CRS, an on-target effect of the treatment that may occur when the engineered cells become activated in the patient's body. CRS was managed globally using prior site education and implementation of the CRS treatment algorithm. Within eight weeks of treatment, 18% of patients experienced grade 3 or 4 neurologic events. There were no incidents of cerebral edema. The most common neurologic events were encephalopathy (34%), headache (37%), delirium (21%), anxiety (13%) and tremor (9%).

Novartis Leadership in Immuno-OncologyNovartis is at the forefront of investigational immunocellular therapy and was the first pharmaceutical company to significantly invest in CAR-T research, work with pioneers in CAR-T and initiate global CAR-T trials. Kymriah, the first approved CAR-T cell therapy, is the cornerstone of this strategy. Active research programs are underway targeting other hematologic malignancies and solid tumors, and include efforts focused on next generation CAR-Ts that involve simplified manufacturing schemes and gene edited cells.

In April 2017, the FDA granted Breakthrough Therapy designation to CTL019 based on data from the JULIET study, the first multi-center global registration study for CTL019 in adult patients with r/r DLBCL.

About ALLALL is a cancer of the lymphocytes, a type of white blood cell involved in the body's immune system. In people with ALL, the abnormal cells crowd other types of cells in the bone marrow, preventing the production of red blood cells (which carry oxygen), other types of white blood cells and platelets (parts of the blood needed for clotting). As a result, those with ALL may be anemic, more likely to get infections and bruise or bleed easily [4].

ALL comprises approximately 25% of cancer diagnoses among children under 15 years old and is the most common childhood cancer in the US [5]. Despite overall improvements in outcomes of pediatric/young adult B-cell ALL, effective treatment options for patients that have relapsed or are refractory to treatment are limited [6],[7],[8].

Kymriah(TM) (tisagenlecleucel) Important Safety informationThe full prescribing information, including Boxed WARNING, for Kymriah can be found at:https://www.pharma.us.novartis.com/

Kymriah may cause side effects that are fatal or life-threatening, such as Cytokine Release Syndrome (CRS) or Neurological Toxicities. Patients with CRS may experience symptoms including high fever, difficulty breathing, chills/shaking chills, severe nausea, vomiting and diarrhea, severe muscle or joint pain, very low blood pressure or dizziness/lightheadedness. Patients may be admitted to the hospital for CRS and treated with other medications. Patients with neurological toxicities may experience symptoms such as altered or decreased consciousness, headaches, delirium, confusion, agitation, anxiety, seizures, difficulty speaking and understanding, or loss of balance. Patients should be advised to call their health care provider or get emergency help right away if they experience any of these signs and symptoms of CRS or neurological toxicities.

Because of the risk of CRS and neurological toxicities, Kymriah is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called Kymriah REMS.

Serious allergic reactions, including anaphylaxis, may occur after Kymriah infusion. Kymriah can increase the risk of life-threatening infections that may lead to death. Patients should be advised to tell their health care provider right away if they develop fever, chills, or any signs or symptoms of an infection.

Patients may experience prolonged low blood cell counts (cytopenia), where one or more types of blood cells (red blood cells, white blood cells, or platelets) are decreased. The patient's health care provider will do blood tests to check all of their blood cell counts after treatment with Kymriah. Patients should be advised to tell their health care provider right away if they get a fever, are feeling tired, or have bruising or bleeding.Patients may experience hypogammaglobulinemia, a condition in which the level of immunoglobulins (antibodies) in the blood is low and the risk of infection is increased. It is expected that patients may develop hypogammaglobulinemia with Kymriah, and may need to receive immunoglobulin replacement for an indefinite amount of time following treatment with Kymriah. Patients should tell their health care provider about their treatment with Kymriah before receiving a live virus vaccine. After treatment with Kymriah, patients will be monitored life-long by their health care provider, as they may develop secondary cancers or recurrence of their leukemia.Patients should not drive, operate heavy machinery, or do other dangerous activities for 8 weeks after receiving Kymriah because the treatment can cause temporary memory and coordination problems, including sleepiness, confusion, weakness, dizziness and seizures.Some of the most common side effects of Kymriah included: difficulty breathing, fever (100.4F/38C or higher), chills/shaking chills, confusion, severe nausea, vomiting and diarrhea, severe muscle or joint pain, very low blood pressure, and dizziness/lightheadedness. However, these are not all of the possible side effects of Kymriah. Patients should talk to their health care provider for medical advice about side effects.Prior to a female patient starting treatment with Kymriah, their health care provider may do a pregnancy test. There is no information available for Kymriah use in pregnant or breast-feeding women. Therefore, Kymriah is not recommended for women who are pregnant or breast feeding. If either sex partner has received Kymriah, patients should talk to their health care provider about birth control and pregnancy.Patients should tell their health care provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.After receiving Kymriah, patients should be advised that some commercial HIV tests may cause a false positive test result. Patients should also be advised not to donate blood, organs, or tissues and cells for transplantation after receiving Kymriah.

DisclaimerThis press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as "pioneering," "commitment," "breakthrough," "mission," "is establishing," "will," "investigational," "step forward," "may," "are creating," "next wave," "eager to progress," "committed," "is working to," "plans," "later this year," "anticipated," "would," "under discussion," "potential," "look forward to," "potentially," "strategy," "underway," "efforts," "focused on," "next generation," "continues to advance," "continue to invest," "Breakthrough Therapy designation," or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for Kymriah and the other investigational products described in this press release, regarding our ability to implement, scale and sustain commercial manufacturing for Kymriah or the other investigational products described in this press release, regarding our ability to build a network of treatment centers to offer Kymriah or the other investigational products described in this press release, regarding the potential future success of patient support programs or patient access solutions for Kymriah or of the collaboration with CMS to establish indication-based pricing and outcomes-based payments for CAR-T cell therapies, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that Kymriah or the other investigational products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Neither can there be any guarantee that Novartis will secure continued approval for Kymriah or the other investigational products described in this press release following accelerated approval. Nor can there be any guarantee that Novartis will successfully implement, scale and sustain commercial manufacturing for Kymriah or the other investigational products described in this press release, or successfully build a network of treatment centers to offer Kymriah or the other investigational products described in this press release. Neither can there be any guarantee that Novartis will successfully implement patient support programs or patient access solutions for Kymriah or the other investigational products described in this press release, or that the collaboration with CMS to establish indication-based pricing and outcomes-based payments for CAR-T cell therapies will be successful or achieve its intended goals. Nor can there be any guarantee that Kymriah or the other investigational products described in this press release will be commercially successful in the future. In particular, our expectations regarding Kymriah and such other investigational products could be affected by, among other things, our ability to successfully implement, scale and sustain commercial manufacturing and build a network of treatment centers; our ability to successfully implement patient support programs and patient access solutions; our ability to secure continued approval following accelerated approval; our ability to successfully establish indication-based pricing and outcomes-based payments for CAR-T cell therapies in collaboration with CMS; the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures; general economic and industry conditions, including the effects of the persistently weak economic and financial environment in many countries; safety, quality or manufacturing issues, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About NovartisNovartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic and biosimilar pharmaceuticals and eye care. Novartis has leading positions globally in each of these areas. In 2016, the Group achieved net sales of USD 48.5 billion, while R&D throughout the Group amounted to approximately USD 9.0 billion. Novartis Group companies employ approximately 119,000 full-time-equivalent associates. Novartis products are sold in approximately 155 countries around the world. For more information, please visit http://www.novartis.com.

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References[1] Kymriah (tisagenlecleucel) Prescribing information. East Hanover, New Jersey, USA: Novartis Pharmaceuticals Corporation; August 2017.[2] Ronson, A., Tvito, A., Rowe, JM., "Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia in Adults." Current Oncology Reports, 2016 Jun;18(6):39. https://www.ncbi.nlm.nih.gov/pubmed/27207612. Accessed August 4, 2017.[3] Leukemia & Lymphoma Society, "Acute Lymphoblastic Leukemia." https://www.lls.org/leukemia/acute-lymphoblastic-leukemia/treatment/relapsed-and-refractory. Accessed August 4, 2017.[4] National Cancer Institute, "Childhood Acute Lymphoblastic Leukemia Treatment (PDQ) - Patient Version." https://www.cancer.gov/types/leukemia/patient/child-all-treatment-pdq#link/_1. Accessed August 4, 2017.[5] Howlader, N., Noone, A.. M, Krapcho, M., et al. SEER Cancer Statistics Review, 1975-2010. National Cancer Institute, April 2013; Section 28.9 (12).[6] Oudot, C.., Auclerc, F.., Levy, V., et al. Prognostic Factors for Leukemia Induction Failure in Children With Acute Lymphoblastic Leukemia and Outcome After Salvage Therapy: The FRALLE 93 Study. Journal of Clinical Oncology, March 2008; Volume 28 (9).[7] Chessels, J., Veys, P., Kempski, H., et al. Long-term follow-up of relapsed childhood acute lymphoblastic leukaemia. British Journal of Hematology, 2003; 123 (3).[8] Reismuller, B., Peters, C., Dworzak, M., et al. Outcome of children and adolescents with a second or third relapse of acute lymphoblastic leukemia (ALL): a population-based analysis of the Austrian ALL-BFM (Berlin-Frankfurt-Mnster) Study Group. Journal of Pediatric Hematology/Oncology. July 2013; 35 (5).

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Novartis receives first ever FDA approval for a CAR-T cell therapy, Kymriah(TM) (CTL019), for children and young ... - GlobeNewswire (press release)

Calimmune Inc., a gene-therapy drug startup company co-founded by a University of Arizona alumnus, will be acquired by Australian-based biotech drug giant CSL Ltd. for $91 million.

The deal, which will make Calimmune part of Pennsylvania-based CSL Behring, also includes up to $325 million in potential performance based milestone payments over eight or more years after the transactions close, expected within the next two weeks.

Calimmune, co-founded by UA biology grad and entrepreneur Louis Breton in 2006, is developing stem-cell gene therapy to strengthen patients own immune systems.

The companys technology is based on research by co-founder and Nobel Prize winner David Baltimore of the California Institute of Technology, Irvin Chen of UCLA and Inder M. Verma of the Salk Institute for Biological Studies.

Calimmunes clinical and laboratory operations are based in Pasadena, California, and Sydney, Australia, while its corporate office is in Tucson.

In 2013, Calimmune won an $8.3 million grant from the California Institute for Regenerative Medicine to study its HIV drug. Its lead drug candidate is in Phase I/II clinical trials as a one-time treatment to prevent HIV progression to AIDS.

The acquisition will give CSL Behring Calimmunes pre-clinical drug candidate, CAL-H, a stem-cell gene therapy for the treatment of sickle cell disease and blood disorders, complementing the companys current product portfolio, CSL said.

The deal also includes two proprietary Calimmune technologies to select genetically modified stem cells and to produce viruses used to deliver gene therapy.

CSL Ltd. CEO Paul Perreault said the acquisition will boost his companys growth in gene therapy, calling Calimmunes accomplishments thus far impressive.

While Calimmune is still in the early stages, we believe that our combined strengths have tremendous potential to change treatment paradigms, and most importantly, significantly improve the lives of our patients, Perreault said in a news release.

Breton, Calimmunes CEO, said CSL is an established global leader in protein-replacement therapies, with a track record of driving new treatments to the global marketplace.

Together, we are well positioned to take our achievements to the next level, Breton said.

In 2015, Calimmune completed a $15 million Series B financing round, led by a large pharmaceutical company.

Members of Tucsons Desert Angels investment group also provided early private-equity funding for the company.

CSL is one of the biggest biotech drug companies in the world, with fiscal 2016 revenue of $6.1 billion.

About 40 percent of the companys revenues come from immunoglobulin products used to treat immunodeficient patients, while it also markets products such as vaccines and antivenins and operates CSL plasma-collection centers.

Contact senior reporter David Wichner at dwichner@tucson.com or 573-4181. On Twitter: @dwichner

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Tucson's Calimmune to be acquired by Australian drug giant - Arizona Daily Star

Since the beginning of 2014, numerous studies have been published looking at using stem cell research and their components to aid hair regrowth and ultimately assist in the effective treatment of hair loss. Currently in the experimental stages, researchers believe that a treatment for baldness may soon be a reality using stem cells to regrow missing or dying follicles.

Perelman School of Medicine

The school of Medicine at the University of Pennsylvania published results of their study into stem cells, where they describe how they were able to convert adult cells into epithelial stem cells cells that facilitate the regrowth of follicles. The thought of using stem cells to regrow follicles has never been properly experimented on before and the team says they are the first to achieve this result.

How did the team produce the cells?

By adding three genes, the team led by Dr. Xiaowei Xu, converted human skin cells into induced pluripotent stem cells (iPSCs). These stem cells are able to change into any cell types in the body, which means the researchers were able to convert them to those stem cells which are commonly found in part of hair follicles. Dr. Xu was able to force the iPSCs to make large quantities of epithelial stem cells using techniques from other researchers to convert the iPSCs into keratinocytes.

Not ready for practical use yet

Though hair follicles were produced from this experiment, Dr. Xu says there is still a while to go before this can be implemented as remedy to hair loss for patients. This is the first time anyone has made progress of cells that are capable of generating hair follicles adding that the cells could aid in wound healing as well as hair regeneration. However, researchers will still need to determine how to foster the growth of dermal papillae, the other cell that is needed for a healthy hair follicle to grow.

Laboratory of Mammalian Cell Biology and Development

States away, a team at the Laboratory located at the Rockefeller University in New York focused on stem cells in the hair follicle to determine what causes them to switch on naming the signal as Sonic Hedgehog. Led by Ya-Chieh Hsu, the team was able to disable the signal which allowed them to interfere with hair growth and regeneration.

Importance of Sonic Hedgehog

The results of the research concluded that Transit-Amplifying cells (TACs) are able to emit a signal that induces quiet hair follicle stem cells to become active. Once TACs are generated, the stem cell population becomes activated. Although there still needs to more insight into how to control TACs and the Sonic Hedgehog signal, this study can prove to be vital into the manifestations of hair loss, which in the long run can be beneficial when using stem cells to facilitate hair regrowth.

Ashley and Martin currently do not advocate the use of stem cells, however our doctors constantly stay in touch and monitor the latest research and developments in hair loss treatment.

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Hair Regrowth using Stem Cells | Ashley and Martin

Bone marrow contains hematopoetic stem cells, the precursors to every blood cell type. These cells spring into action following bone marrow transplants, bone marrow injury and during systemic infection, creating new blood cells, including immune cells, in a process known as hematopoiesis.

A new study led by University of Pennsylvania and Technical University of Dresden scientists has identified an important regulator of this process, a protein called Del-1. Targeting it, the researchers noted, could be an effective way to improve stem cell transplants for both donors and recipients. There may also be ways to modulate levels of Del-1 in patients with certain blood cancers to enhance immune cell production. The findings are reported this week in The Journal of Clinical Investigation.

Because the hematopoetic stem cell niche is so important for the creation of bone marrow and blood cells and because Del-1 is a soluble protein and is easily manipulated, one can see that it could be a target in many potential applications, said George Hajishengallis, the Thomas W. Evans Centennial Professor in the Department of Microbiology in Penns School of Dental Medicine and a senior author on the work.

I think that Del-1 represents a major regulator of the hematopoetic stem cell niche, said Triantafyllos Chavakis, co-senior author on the study and a professor at the Technical University of Dresden. It will be worthwhile to study its expression in the context of hematopoetic malignancy.

For Hajishengallis, the route to studying Del-1 in the bone marrow began in his field of dental medicine. Working with Chavakis, he had identified Del-1 as a potential drug target for gum disease after finding that it prevents inflammatory cells from moving into the gums.

Both scientists and their labs had discovered that Del-1 was also expressed in the bone marrow and began following up to see what its function was there.

In the beginning, I thought it would have a simple function, like regulating the exit of mature leukocytes [white blood cells] from the marrow into the periphery, Hajishengallis said, something analogous to what it was doing in the gingiva. But it turned out it had a much more important and global role than what I had imagined.

The researchers investigations revealed that Del-1 was expressed by at least three cell types in the bone marrow that support hematopoetic stem cells: endothelial cells, CAR cells and osteoblasts. Using mice deficient in Del-1, they found that the protein promotes proliferation and differentiation of hematopoetic stem cells, sending more of these progenitor cells down a path toward becoming myeloid cells, such as macrophages and neutrophils, rather than lymphocytes, such as T cells and B cells.

In bone marrow transplant experiments, the team discovered that the presence of Del-1 in recipient bone marrow is required for the transplanted stem cells to engraft in the recipient and to facilitate the process of myelopoesis, the production of myeloid cells.

When the researchers mimicked a systemic infection in mice, animals deficient in Del-1 were slower to begin making myeloid cells again compared to those with normal Del-1 levels.

We saw roles for Del-1 in both steady state and emergency conditions, Hajishengallis said.

Hajishengallis, Chavakis and their colleagues identified the protein on hematopoetic stem cells with which Del-1 interacts, the 3 integrin, perhaps pointing to a target for therapeutic interventions down the line.

The scientists see potential applications in bone marrow and stem cell transplants, for both donors and recipients. In donors, blocking the interaction between Del-1 and hematopoetic stem cells could enhance the mobilization of those progenitors into the bloodstream. This could be helpful for increasing donor cell numbers for transplantation. Transplant recipients, on the other hand, may need enhanced Del-1 interaction to ensure the transplanted cells engraft and begin making new blood cells more rapidly.

In addition, people undergoing chemotherapy who develop febrile neutropenia, associated with low levels of white blood cells, might benefit from the role of Del-1 in supporting the production of immune-related blood cells such as neutrophils.

Its easy to think of practical applications for these findings, said Hajishengallis. Now we need to find out whether it works in practice, so our studies continue.

Ioannis Mitroulis, Lan-Sun Chen and Rashim Pal Singh of TU-Dresden were co-lead authors on the study, and Ben Wielockx of TU-Dresden was a co-senior author along with Hajishengallis and Chavakis. They were joined by coauthors Tetsuhiro Kajikawa, Kavita Hosur, Tomoki Maekawa and Baomei Wang of Penn Dental Medicine; Ioannis Kourtzelis, Matina Economopoulou, Maria Troullinaki, Athanasios Ziogas, Klara Ruppova, Pallavi Subramanian, Panayotis Verginis, Malte Wobus, Martin Bornhuser and Tatyana Grinenko of TU-Dresden; Torsten Tonn of the German Red Cross Blood Donation Service in Dresden; and Marianna Di Scala and Andrs Hidalgo of the Spanish National Center for Cardiovascular Research.

The study was supported by the Deutsche Forschungsgemeinschaft, European Commission, European Research Council and National Institutes of Health (grants AI068730, DE024153, DE024716, DE0152 54 and DE026152).

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Bone Marrow Protein May Be Target for Improving Stem Cell Transplants - Penn: Office of University Communications

About five or six years ago, a cousin of mine who is an emergency medical technician in New Jersey told me something quite interesting, We're all worried about terrorists of all kinds foreign, domestic, Arab extremists, and right-wing militias, but a more dangerous and ugly threat is ... drugs.

His cautionary statement was lost on me until a couple of years ago because, for some reason, I didn't think drugs would make inroads to our rural community and its populace. Drug abuse was, in my mistaken mind, a problem of the inner city and not a concern of northwestern Pennsylvania. Anyone with any consciousness knows that I was mistaken.

The number of drug deaths in all of Pennsylvania, according to the Pennsylvania Coroners Association for 2015 was 3,505. Of those deaths, 22 percent (777) were in rural counties like ours and 85 percent of those deaths were a result of the overdose of illegal drugs.

To drill down even further, 55 percent of the illegal drug deaths resulted from heroin and 26 percent from cocaine and the balance from other drugs. Primarily, these deaths are white, single males, but 19 percent are married.

Additionally, the number of hospital admissions in Crawford County for 2015 was 150, slightly lower than admissions for alcohol abuse. Parenthetically, the number of deaths in 2016 and 2017 are well above the 2015 national number of 57,000, and drug overdose is the leading cause of death of people 50 and younger.

It's apparent that we have a problem of serious proportions. What can we do to stem the tide?

In some countries, the government supplies injection studios where the addicted can administer their drugs under supervision and, presumably, be monitored for an overdose. Given the progressive nature of the addiction/disease, this seems to not answer the root causes of the problem and just deals with the ugly outcome of it. We are left with causation of the disease and those factors most assuredly vary with each individual, though there are some causes that go across all individual circumstances.

Some individuals have an addictive personality that pre-disposes them to addictive chemicals like heroin and alcohol, while other people do not as quickly develop dependence. Additionally, some drugs, like heroin, are addictive more quickly and profoundly than others.

Of course, the basis for all behavior, addictive and otherwise, is the human search for pleasure and avoidance of pain or discomfort. So, in the case of opioids, the pleasure is especially deep in their use, the avoidance of pain extremely effective, and in detoxification, the discomfort is particularly acute.

Further, the human brain and central nervous system receptors are conditioned to opioid use and scream for it. What the addict is left with, then, is an extremely powerful physical addiction grounded in neurological and psychological dependence that makes him incapable of the rational decision to not use the drug.

Perhaps, initially, the user can decide to not try the drug, but once addicted it's well nigh impossible to stop without outside intervention. Since opioids bind with receptors in all body cells, including heart and lung, overdose leading to pulmonary and cardiac episodes become a lethal possibility. To never start, then, seems to be the answer to never having to quit or dying of the addiction.

In connection with this, it's incumbent on health care providers to rethink the use of medication containing opioids and thus avoid some medically induced addiction. Are there any concrete answers and if there are, how can a society implement them without hijacking free choice? Everyone has the right to poor judgment, don't they?

Joseph Stalin once remarked, The death of thousands is but a statistic, while the death of one person is a tragedy. So it is with opioid overdose and fatality. The one death is projected upon the mother, father, husband, wife, children, brother, sister or other family and friends of the user/victim and the incomparable pain experienced by them is a human tragedy of immense proportions and as indescribable as the breaking of a human heart.

Society also suffers in the use of valuable resources in the treatment and prevention of addiction but ultimately pays a deep and most grievous price in the loss of human talent and potential.

Everyone loses. Everyone.

Gary DeSantis is a Meadville resident and author of a book titled The 6th Floor.

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COLUMN: Startling statistics concerning drug deaths in rural communities - Meadville Tribune

Photo: Arnold Gold / Hearst Connecticut Media

Dr. Steven Gore at the Advanced Cell Therapy Lab at Smilow Cancer Hospital in New Haven, where cells are manufactured that fight a rare form of leukemia.

Dr. Steven Gore at the Advanced Cell Therapy Lab at Smilow Cancer Hospital in New Haven, where cells are manufactured that fight a rare form of leukemia.

Rare leukemia targeted by modifying patients immune cells

NEW HAVEN >> Young patients with a particular type of leukemia who have relapsed after going into remission may find new hope through a treatment that involves modifying a patients own T cells, an important part of the immune system, to destroy cancer cells.

While the therapy, in which genes are inserted into a patients T cells, is expected to receive Food and Drug Administration approval soon for pediatric patients, researchers hope that it will be effective for adult patients as well and for more types of cancers, according to Dr. Steven Gore, director of hematologic malignancies at the Yale Cancer Center.

The cancer thats the focus of this T cell therapy is B-lineage acute lymphoblastic leukemia, which is the most common leukemia in kids and its commonly cured in the 2- to 10-year-old age group, Gore said. He said about 70 percent of children with the cancer are cured.

However, the rest suffer a recurrence of the disease even after treatment with chemotherapy and stem cell transplants.

Its getting to be a difficult situation, Gore said.

There are 3,100 cases of children with B-lineage ALL each year, he said.

B cells, also known as B lymphocytes, are white blood cells that produce antibodies, which fight infection. A characteristic of B cells is that they have a protein on their surface called CD19, which is the key to the new treatment.

The new process, marketed by Novartis and first developed at the University of Pennsylvania, involves harvesting T cells from the patient. Novartis then introduces DNA into these T cells, introducing new genes into the T cells, [which] include a receptor that will recognize CD19, Gore said. The genes that are fused into the T cells are manufactured in the lab but are copies of normal human genes, Gore said. The new cell is called a chimeric antigen receptor T cell, or CAR-T cell.

Normal T cells fight disease, and we know that T cells can attack cancer cells as well, but getting them to do so in the host where the cancer has developed is tricky, Gore said. Cancer cells are very similar [to] normal cells from which they derive.

Turning the T cells into CAR-T cells helps by targeting the CD19 marker on the B cells. CD19 happens to be a pretty good target for cancer technology because its only on B cells, Gore said. These new CAR-T cells latch onto the leukemia cells.

Reproducing cells

Then, once they see that theyre needed, the CAR-T cells are going to make more of themselves. Theyre going to make a whole army-full beside what we gave the patient, Gore said. Other genes in the introduced DNA give the immune system the go-ahead to kill these leukemia cells.

The CAR-T cells target both healthy and malignant B cells, but people live all the time without B cells, Gore said, by relying on drugs such as rituximab.

The treatment is not easy on the patient, however. When this massive influx of these new T cells attack all these leukemia cells, youre basically setting up a jihad in your body, Gore said. People can get very critically ill after this therapy, even needing to be treated in the intensive care unit.

Despite the hardship, the FDAs Oncologic Drugs Advisory Committee voted 10-0 on July 12 to recommend approval of CAR-T therapy, and it is very rare that an ODAC approval does not end up in an FDA approval, Gore said.

In one trial, 41 of 50 patients with relapsed or refractory B-lineage ALL each achieved complete remission after three months, Gore said, and 60 percent of those patients were still in remission six months later.

It will be rapidly opened up to adults as well, theres no question about it, he said. Some people think this therapy may replace stem cell therapy and doctors hope it can be given before a patient relapses, avoiding stem cell transplants.

We dont have long-term follow-up to know if these patients are cured, Gore said. Theyve certainly been rescued from otherwise-certain death.

Gore said the Yale School of Medicine has been approached by Novartis to be one of the rollout sites for this therapy.

While the new treatment targets a relatively rare cancer, its likely to be effective in other cancers involving B cells, including other types of leukemia and lymphoma, Gore said. (Not all lymphomas and leukemias are B cell cancers, however.) This rare leukemia has been the subject of all this investigation because CD19 is such a low-hanging fruit, because we can live without B cells, he said.

But the technology can theoretically be adapted to any kind of tumor, he said. Theoretically, you could make a CAR-T to target any particular kind of cancer provided that that cancer expresses certain proteins that are predominantly limited to the cancer and not important vital organs.

Call Ed Stannard at 203-680-9382.

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Rare leukemia targeted by modifying patients' immune cells - New Haven Register

n BELMONT UNIVERSITY

TRAVELS ABROAD

Hannah Koss, ofLewisburg, traveled to Spain this summer as part of Belmont Universitys largest group of student travelers in university history. With more than 650 students participating in 34 programs, including Maymester trips, students will spend time in Greece, Brazil, England, France, Switzerland and Haiti, among many other locations.

n GETTYSBURG COLLEGE

SPRING DEANS LIST

Logan Aikey, ofLewisburg;Caitlin Apple, ofLewisburg;Nicole Bhangdia, of Lewisburg;Daniella Snyder,ofNorthumberland

GRADUATE

Caitlin Apple, of Lewisburg, earned a degree in health sciences.

n INDIANA UNIVERSITY OF PENNSYLVANIA

SPRING DEANS LIST

Brandon Michael Cox, of Elysburg; Aaron J. Crawford, of Elysburg; Abby Nicole Menefee,of Elysburg;Frank Austin Manzano, of Milton; Nicole Elizabeth Shoop,of Milton;Marisa Ann Montgomery, of Mount Carmel;Leah M. Gardner, of Northumberland;Erin L. Moser, of Paxinos; Brett William Rebuck,of Paxinos;Bridgette Anne Hine, of Shamokin; Maggie Florence Kushner,of Shamokin;Alexandria Paige Seidel,of Turbotville;Elaina Katherine Bower, of Watsontown;Makayla Lyn Finan, of Watsontown; Christopher Hayes Schaeffer, of Watsontown

n ITHACA COLLEGE

SPRING DEANS LIST

Kelly Csernica, of Lewisburg;Abigail Wolfe, of Selinsgrove

n PENNSYLVANIA COLLEGE OF TECHNOLOGY

MEDICAL TEAM

A large group of Pennsylvania College of Technology students is set to join the medical team at the 2017 Little League Baseball World Series in South Williamsport this August.

The students are pursuing careers as physician assistants and paramedics. During the 11-day tournament, they will serve both participants and spectators of the series, which draws 16 teams from around the world, and tens of thousands of fans each day.

Areaphysician assistant student volunteers: Michelle D. Detwiler, of Milton; Catherine A. Fisher, of Elysburg; Montanah R. James, of Danville; James T. Kane II, of Danville; Danielle M. Klock, of Sunbury; Kaitlyn R. McCaffery, of New Columbia; Jonathan E. Mitchell, of Middleburg; Kurstyn T. Pfleegor, of Northumberland; Angela R. Vought, of Elysburg

Area emergency medical services and paramedic technician student volunteers: Matthew S. Walter, of Mifflinburg; Sarah A. Zimmerman, of Turbotville

n SUSQUEHANNA UNIVERSITY

INTERN

Marissa Heddings, of Selinsgrove,recently served an internship at Heddings Insurance.

Heddingss responsibilities included using the agencys software anddatabase to calculate data and information for clients. Through the courseof the internship, she gained experience learning insurance policies andgaining experience interacting with customers.

Heddings is a finance major. A 2014 graduate ofSelinsgrove Area High School, she is the daughter of Clair and LoriHeddings.

Nicole Krebs, of Selinsgrove, is serving an internship this summer at Evangelical Community Hospital.

Krebss responsibilities include job shadowing nine different departments at the hospital. Through the course of the internship, she will gain experience gaining learning experience from being exposed to work in the medical field close-up.

Krebs is a neuroscience major. A 2015 graduate of Selinsgrove Area High School, she is the daughter of Mark Krebs and Yvonne Krebs.

INDUCTED

Local residents were among the 20 studentswho were recently inducted into the Kappa Delta Pi honor society atSusquehanna University.

Kappa Delta Pi is an honor society for educators and future educators. Thepurpose of the society is to promote excellence in and recognize outstandingcontributions to education.

Kelsey Kline, of Selinsgrove, is an early childhood education major. A 2012 graduate of Selinsgrove Area HighSchool, she is the daughter of Mark and Melissa Kline.

Brynn Musser, of Selinsgrove, is an early childhood education and psychologymajor. A 2012 graduate of SelinsgroveArea High School, she is the daughter of Todd and Pam Musser.

Jessica Portzline, of Mount Pleasant Mills, is a music education major. A 2014 graduate of Midd-West High School, sheis the daughter of Melissa Portzline.

Jenna Yarger, of Middleburg, is a biochemistry major. A 2014 graduate of Midd-West High School, she is the daughterof Rodney Yarger and Paula Schick.

Thirty-seven students were inducted into theOmicron Delta Kappa leadership honor society at Susquehanna University.

Omicron Delta Kappa, a national leadership honorary organization, recognizesjuniors and seniors who have achieved in and out of the classroom.

Brandy Shrawder, of Mifflinburg, is a biology and French major. A 2014 graduate of Mifflinburg Area High School, she is thedaughter of Ralph and Vickie Shrawder.

Julie Lentz, of Lewisburg, is a communications-digitalmultimedia-broadcasting major. A 2014 graduate ofLewisburg Area High School, she is the daughter of Ronald Lentz Jr. and LoriMoyer.

Ryan Keller, of Turbotville, was inducted into Kappa Mu Epsilon mathematics honor society at Susquehanna University

Kappa Mu Epsilon chapters are located in colleges and universities of recognized standing which offer a strong mathematics major. Members are selected from students of mathematics and other closely related fields who have maintained standards of scholarship, have professional merit and have attained academic distinction. The Susquehanna chapter was chartered in 1969.

Keller is a computer science major. A 2015 graduate of Warrior Run High School, he is the son of Mark and Jode Keller.

Vanessa Lloyd, of Lewisburg, was inducted into Sigma Alpha Iota music fraternity at Susquehanna University.

Sigma Alpha Iota (SAI) is a music fraternity for women that strives to promote the development and growth of music across campus and even across the world. The sisters of SAI serve as volunteer ushers for various events sponsored by Susquehanna Universitys Department of Music. The organizations projects and events are all music-oriented and have included fundraisers for VH1s Save the Music organization. Chapter membership is open to students of all majors.

Lloyd is a music education-instrumental major. A 2016 graduate of Mifflinburg Area High School, she is the daughter of Shawn and Susan Lloyd.

RESEARCH

Several local students are spending thesummer conducting research with faculty at Susquehanna University.Susquehannas distinctive Summer Research Partners program is a uniqueopportunity for students to actively participate in a research project on afull-time basis. Faculty members serve as mentors to the students, workingone-on-one or in small groups, creating a lively, engaged community oflearners at the university. Since the program began in 1996, more than 100students have taken part in such projects as identifying bacteria at thesite of the Centralia mine fire; studying the behavior of wolf spiders; andmonitoring local waterways, including the nearby Susquehanna River.

Andrew Steely, of Catawissa, is conducting research under the supervision ofAssistant Professor of Physics Carl Faust, concerning atomic molecular andoptical (AMO) physics. Steely is a physics and chemistry major. A 2014 graduate of Southern Columbia Area High School, he is theson of Jay and Anita Steely.

Hannah Sage, of Catawissa, is conducting research under the supervision ofAssistant Professor of Physics Massooma Pirbhai, concerning nanotubes. Sageis a mathematics and physics major. A 2016 graduate ofSouthern Columbia Area High School, she is the daughter of Leigh Geary andTom Sage.

Julia Spear, of Milton, is conducting research under the supervision ofAssistant Professor of Biology Pavithra Vivekanand, concerning thedifferentiation of midline somatic follicle cells and follicle stem cellrenewal. Spear is a biology- secondary education major.A 2014 graduate of Milton Area High School, she is the daughter of James andDonna Spear.

Brandy Shrawder, of Mifflinburg, is conducting research under thesupervision of Assistant Professor of Biology Pavithra Vivekanand,concerning the differentiation of midline somatic follicle cells andfollicle stem cell renewal. Shrawder is a biology and French major. A 2014 graduate of Mifflinburg Area High School, she is thedaughter of Ralph and Vickie Shrawder.

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Campus achievement - Sunbury Daily Item

Three Girl Scouts go for the gold and get it!

Three Girl Scouts from La Jolla received their Gold Awards (the highest honor bestowed for a sustainable act of service) during an award ceremony June 17. La Jolla High School students Nora Joyce, Aurora de Tagyos and Maia Hayden were recognized for their projects, designed to take action and demonstrate leadership when girls address the root cause of an issue; build and oversee a volunteer team; meet measurable goals; and change peoples beliefs, attitudes, assumptions and behavior.

According to Girl Scout reports, here is a summary of each girls projects:

Backyard Bounty by Aurora de Tagyos: After noticing that fruit from trees in my neighborhood was going to waste, I organized and trained a team to harvest excess food from area gardens. We gleaned 1,200 servings of fresh produce to donate to struggling families.

Self-Defense for Women by Maia Hayden: As a first-degree black belt and lifelong martial arts student, I am passionate about self-defense. I held classes for young women in high school and college, as well as women who have experience with assault, and made a video demonstrating basic moves.

Leadership Through Lacrosse by Nora Joyce: The Preuss School, which serves students from lower income families, didnt have middle school or junior varsity lacrosse teams. I set up beginner-level clinics where girls got a head start toward the confidence, strength and can-do spirit playing varsity will bring them.

Courtesy

Girl Scout Gold Award recipient Aurora de Tagyos

Girl Scout Gold Award recipient Aurora de Tagyos (Courtesy)

The Society of Professional Journalists, San Diego Chapter held its annual awards reception July 19 at the Kona Kai Resort & Spa when La Jolla Light brought home five, First Place reporting awards for the following stories:

The La Jolla Light has an immediate opening for an experienced reporter. The non-exempt full-time position includes vacation, healthcare and other benefits. The job entails covering civic meetings, crime incidents and taking photos, and posting stories on our website. If interested and qualified, send a query letter and resume to editor@lajollalight.com

The first edition of The San Diego Festival of Books 10 a.m. to 6 p.m. Saturday, Aug. 26 at Liberty Station will feature 40 local authors participating in talks and book signings. La Jollas Warwicks Bookstore will be there providing support and selling the books. We will have a booth and that will give us an opportunity to present our store and highlight what we do within the community, said Warwicks book buyer Adrian Newell to La Jolla Light.

Organized by The San Diego Union-Tribune, the festival goal is to create a space for the reading community in San Diego. As technology becomes more and more prevalent, its great to have something that focuses on the printed word, Newell said. A speakers lineup will be announced at sdfestivalofbooks.com

Bridget Burton donated 50 of her recently published childrens books titled, Annie Kai Lani Kai Lou: Kauais Beloved Pup (and accompanying CD), to young patients at Rady Childrens Hospital. I wanted to share this fun, sing-along book with kids who are facing some serious challenges, said Burton, a resident of La Jolla.

The whimsically illustrated book features the adventuresome Springer Spaniel Annie Kai Lani Kai Lou in a range of activities that all families can experience on the island of Kauai. Annie golfs with a view of the ocean, canoes on the Wailua River, surfs at Poipu Beach, and even watches re-runs of Jurassic Park at the Grand Hyatt on Kauai. anniekailani.com

Torrey Pines Elementary School Foundation (TPESF) received a $9,600 grant from the Monsanto San Diego Research Facility to expand and enrich its garden program to deepen student understanding of the life sciences. Specifically, funds will be used to integrate a garden science curriculum for all grade levels, provide opportunities for individual student experiments, and expand and maintain the current garden infrastructure including raised beds and the greenhouse.

Courtesy

Garden coordinator and TPES parent, William Jenkins, Ph.D.

Garden coordinator and TPES parent, William Jenkins, Ph.D. (Courtesy)

This grant is critical for the continued growth and success of our Science in the Garden Program. Under the leadership of parent William Jenkins, Ph.D., and science teacher Cathy Isom, our program combines elements of basic science, innovative technology, and critical thinking that are essential to developing the leaders who will be tasked to solve the challenges facing our planet, said Neha Bahadur, M.D., TPESF past-president.

TPESF previously received a Monsanto Fund site grant in 2016. These initial funds helped to solidify the infrastructure of the Science in the Garden program by supporting teacher training and curriculum development, science supplies including a digital microscope, and a large greenhouse and planting beds.

Registration is open for La Jolla Christian Fellowships summer camp, which is open to participants from any denomination. Dates for high school students July 30-Aug. 4; Middle School Aug. 6-11. Contact Pastor Harry Wilson at harry@lajollcf.org for pricing details.

Bird Rocks Capricorn Boutique will close its doors Aug. 25 after 10 years at 5628 La Jolla Blvd. Owners Krissy Heinz and Lisa Ovadia emailed a notice announcing the closure.

It is with both sadness and joy that we share this news, that after nearly 11 wonderful years, we are ready to begin the next chapter of our lives. We cannot express the gratitude we have for the years of continued love and support you have shown us. Many of you are like family to us and we will cherish the bonds we have formed over the years. There are so many special memories that will remain in our hearts always, it reads.

The three sole female full professors at Salk Institute, the highest possible rank for faculty members, are suing the research center in two different lawsuits for allegedly giving preference to men in pay, promotion, grant funding and leadership positions.

Salk biologists Vicki Lundblad and Katherine Jones announced their legal action earlier this month. As a response, Salk officials rejected the claims and asserted that both scientists trailed their peers in their work. Then, Beverly Emerson, a prominent biochemist who studies how genes contribute to disease, filed a second lawsuit against what she describes as an antiquated boys club.

Nobel Laureate Elisabeth Blackburn, president of the Salk Institute, wrote in a statement: I would never preside over an organization that in any way condones, openly or otherwise, the marginalization of women scientists.

The California Institute for Regenerative Medicine (CIRM) awarded $5.8 million to fund UC San Diegos stem cell research to develop a new variation of cancer immunotherapy.

UCSDs Moores Cancer Center physicians led by Ezra Cohen will try to adapt CAR T-cell therapy, pioneered by Dr. Carl June at the University of Pennsylvania, to fight cancers stem cells. The treatment has been used against blood cancers, with a number of patients experiencing dramatic and long-lasting remissions.

CIRM was created in 2004 by California voters with $3 billion in funding to accelerate stem cell research and treatments.

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La Jolla Light News Nuggets: July 27 - La Jolla Light

The 2016 Scientific Committee Sessions will be held Saturday, December 3, and Sunday, December 4. Each session will be offered twice. A question-and-answer period will occur at the end of each individual speaker presentation. Invited abstracts of these sessions will be published in the Program Book and on the flash drive containing the annual meeting abstracts.

All Scientific Program sessions will be recorded and made available through ASH On Demandafter the meeting.

Robert Brodsky, MD The Johns Hopkins University School of Medicine Baltimore, MD

Ross Levine, MD Memorial Sloan-Kettering Cancer Center New York, NY

Jump to:

(Select) Ad Hoc Scientific Committee on Epigenetics and Genomics Joint Session: Scientific Committee on Blood Disorders in Childhood and Scientific Committee on Red Cell Biology Joint Session: Scientific Committee on Hematopoiesis and Scientific Committee on Myeloid Biology Scientific Committee on Bone Marrow Failure Scientific Committee on Hematopathology and Clinical Laboratory Hematology Scientific Committee on Hemostasis Scientific Committee on Immunology and Host Defense Scientific Committee on Iron and Heme Scientific Committee on Lymphoid Neoplasia Scientific Committee on Myeloid Neoplasia Scientific Committee on Plasma Cell Neoplasia Scientific Committee on Platelets Scientific Committee on Stem Cells and Regenerative Medicine Scientific Committee on Thrombosis and Vascular Biology Scientific Committee on Transfusion Medicine Scientific Committee on Transplantation Biology and Cellular Therapies

Enhancers and Chromatin Landscapes in Development and Cancer

Dr. Majeti will focus on chromatin accessibility patterns during normal humanhematopoiesis and AML evolution from pre-leukemic HSCs with a detailed discussion ofcohesin complex mutants.

Dr. Aifantis will focus on how higher order chromosomal structure is altered in leukemia and how key regulators of this process are involved in hematopoietic function and gene expression.

Dr. Ren will present data on state-of-the-art approaches to map human genomic architecture and how this process is altered during malignant transformation.

Please click here to review this session.

AshAlizadeh,MD, PhD Stanford University Stanford,CA

BingRen,PhD University of San Diego La Jolla,CA Organization and Regulation of the Human Genome

IannisAifantis,PhD New York University New York,NY The Impact of 3D Chromosomal Topology in Acute Leukemia

RaviMajeti,MD, PhD Stanford University Stanford,CA Chromatin Accessibility Charts Human Hematopoiesis and Acute Myeloid Leukemia Evolution

Understanding and Repairing Faulty Red Blood Cells

Dr. Dean will focus on the biology of enhancers, gene regulatory elements that regulate transcription through long-range interactions with promoter regions and have highly tissue-specific functions, including in erythroid cells, as well as roles in promoting pathologic gene expression in disease states.

Dr. Lodish will present ongoing work focused on harnessing an integrative, mechanistic understanding of erythroid progenitor cell signaling pathways that control self-renewing cell divisions to envision novel therapies for anemias.

Dr. De Franceschi will describe the development of non-gene therapy strategies for clinical application, including approaches currently under clinical evaluation.

Dr. Cavazzana will present novel therapeutic approaches in an effort to cure the more prevalent inherited blood diseases worldwide. Results of ongoing clinical trials as well as of promising gene editing strategies will be summarized.

Please click here to review the session.

ColleenDelaney,MD, MSc Fred Hutchinson Cancer Research Center Seattle,WA

Alex C.Minella,MD BloodCenter of Wisconsin Milwaukee,WI

AnnDean,PhD National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health Bethesda,MD New Concepts in Genome Regulation

HarveyLodish,PhD Whitehead Institute for Biomedical Research Cambridge,MA PPARa Agonists and TGF Inhibitors Stimulate Red Blood Cell Production by Enhancing Self-Renewal of BFU-E Erythroid Progenitors

LuciaDe Franceschi,MD University of Verona Verona,Italy New Therapeutic Options: Alternates to Gene Therapy for Treating Hemoglobinopathies

MarinaCavazzana,MD, PhD Hpital Necker Enfants Malades Paris,France Gene Therapy Studies in Hemoglobinopathies: Successes and Challenges

Clonal Development of Hematopoietic Stem Cell Specification and Differentiation at Single Cell Resolution

Dr. Dick will describe clonal evolution of human hematopoiesis at single cell resolution.

Dr. Gottgens will present single cell molecular profiling experiments that reveal new aspects of blood stem cell regulation and their perturbation by leukemic factors.

Dr. Rothenberg will present a systems biology level understanding of the transcription networks that control lymphoid cell fate decisions.

Dr. Schroeder will present his work using transcription factor reporters to track myeloid lineage fate determination, and the instructive role of niche and environmental factors.

Please click here to review this session

YiZheng,PhD Cincinnati Children's Hospital Cincinnati,OH

H. LeightonGrimes,PhD Cincinnati Children's Hospital Cincinnati,OH

John E.Dick,PhD University Health Network Toronto,ON,Canada Molecular Events Defining Human Clonal Hematopoiesis at Single Cell Resolution

BertieGottgens,DPhil University of Cambridge Cambridge,United Kingdom Defining Cellular States, Differentiation Trajectories, and Regulatory Networks Through Single Cell Profiling

EllenRothenberg,PhD California Institute of Technology Pasadena,CA Transcription Factor Gene Fluorescent Reporters Track Lineage Fate in Lymphoid Commitment

TimmSchroeder,PhD ETH Zurich Basel,Switzerland Long-term Live Single Cell Quantification of Transcription Factor Dynamics

Ribosomes and Ribosomopathies

Dr. Barna will introduce the concept that not all ribosomes are created equal, and that translation by specialized ribosomes represents a separate layer of gene regulation that determines which mRNAs are effectively translated. Her work provides insights into how mutations in different ribosome proteins lead to a diverse spectrum of clinical features.*Please note that Dr. Barna will only be speaking at the Saturday session.*

Dr. Warren will provide structural insights into the mechanism by which mutations that cause Schwachman-Diamond anemia affect ribosome assembly.

Dr. Zon will describe a zebrafish model of Diamond Blackfan Anemia, and how chemical suppressor screens may lead to the discovery of novel therapeutics to ameliorate clinical aspects of the syndrome.

Please click here to review the session.

NancySpeck,PhD University of Pennsylvania Perelman School of Medicine Philadelphia,PA

MariaBarna,PhD Stanford University Stanford,CA Specialized Ribosomes: A New Frontier in Gene Regulation, Organismal Biology, & Evolution

Alan J.Warren,MD, PhD University of Cambridge Cambridge,United Kingdom Shwachman-Diamond Syndrome and the Quality Control of Ribosome Assembly

Leonard I.Zon,MD Harvard Medical School, Boston Childrens Hospital Cambridge,MA Modeling Diamond Blackfan Anemia and Developing Therapeutics

Minimal Residual Disease in Hematology: Why, When, and How?

Dr. Wood will describe the key immunophenotypic principles that underlie minimal residual disease detection by flow cytometry and illustrate their application and clinical significance to the monitoring of acute leukemia.

Dr. Valk will discuss minimal residual disease detection in acute myeloid leukemia by means of polymerase chain reaction approaches using the multitude of available molecular markers in the context of clonal hematopoiesis.

Dr. Druley will focus on current strategies for using RNA sequencing as a modality for minimal residual disease detection. As we now move into the era of single-cell transcriptomes and error-corrected sequencing, we may move beyond simple quantitation of chromosomal rearrangements to identify also allele- and transcript-specific profiles of cancer cells as a tool for diagnostics, therapy and mechanistic understanding.

Please click here to review the session.

TorstenHaferlach,MD MLL Munich Leukemia Laboratory Munich,Germany

BrentWood,MD, PhD Seattle Cancer Care Alliance Seattle,WA Multiparameter Flow Cytometry as a Powerful Tool

PeterValk,PhD Erasmus University Medical Center Rotterdam,Netherlands Molecular Minimal Residual Disease Detection in Acute Myeloid Leukemia

Todd E.Druley,MD, PhD Washington University School of Medicine in St. Louis St. Louis,MO Novel Technologies to Detect Minimal Residual Disease

Emerging Therapeutics to Alter Hemostasis and Thrombosis

Dr. Lenting will describe studies of the molecular interactions between factor VIII and von Willebrand factor. Detailed understanding of these interactions has recently been uncovered and can be used for development of improved long-acting factor VIII replacement therapies for treatment of hemophilia A.

Dr. Arruda will describe the discovery and biochemical characterization of factor IX Padua and translational studies. This form of factor IX has enhanced procoagulant activity and is being advanced into gene therapy trials for treatment of hemophilia B.

Dr. Coughlin will describe the discovery and characterization of protease-activated receptors (PARs). The work explained how the coagulation protease thrombin activates platelets and other cells and led to the development of the platelet inhibitory drug, vorapaxar. A crystal structure of a PAR-vorapaxar complex has helped to explain properties of the drug.

Please click here to review this session.

AlanMast,MD, PhD BloodCenter of Wisconsin Milwaukee,WI

Peter JLenting,PhD French Institute of Health and Medical Research (INSERM) Le Kremlin-Bictre,France Von Willebrand Factor Interaction with FVIII: Development of Long Acting FVIII Therapies

ValderArruda,MD, PhD The Children's Hospital of Philadelphia, University of Pennsylvania Philadelphia,PA Factor IX Padua: From Biochemistry to Gene Therapy

ShaunCoughlin,MD, PhD University of California San Francisco San Francisco,CA PAR1 Antagonists Development and Clinical Utility

Innate Immunity: The Green Light to Adaptive Responses

Dr. Trinchieri will discuss the role of inflammation, innate resistance and commensal microbiota in carcinogenesis, cancer progression and cancer therapy.

Dr. Gajewski will discuss innate immune sensing of cancer via the host Stimulator of INterferon Genes (STING) pathway and how this presents therapeutic opportunities to activate effective anti-tumor immunity.

Please click here to review the session.

StanleyRiddell,MD Fred Hutchinson Cancer Research Center Seattle,WA

GiorgioTrinchieri,MD National Cancer Institute, National Institutes of Health Bethesda, Innate Immune Signaling in Regulation of Immunity

ThomasGajewski,MD, PhD University of Chicago Medical Center Chicago,IL Innate Immune Sensing in Anti-Tumor Immunity and Cancer Immunotherapy

From Iron Trafficking to Iron Traffic Jam

Dr. Carlomagno will discuss recent findings on the importance of ferritinophagy to maintain iron homeostasis in vivo. She will also present new data on the role of iron in regulating cell cycle progression and genome stability

Dr. Lakhal-Littleton will discuss the studies in tissue-specific and global hepcidin/ferroportin gene knockouts;offering insight into the interplay between cellular and systemic mechanisms in the regulation of iron levels in the heart and in its healthy functioning. Her studies raise the possibility that the hepcidin/ferroportin axis may also be important in other hepcidin and ferroportin-expressing tissues such as the kidney, the brain and the placenta.

Dr. Knutson will present recent insights from studies of knockout mouse models that aim to identify how various cells and organs, including the heart, take up non-transferrin-bound iron.

Please click here to review this session.

Maria DomenicaCappellini,MD University of Milan - Fondazione iRCCS Ca' Granda Ospedale Policlinico Milan Milan,Italy

FrancescaCarlomagno,MD, PhD Federico II University of Naples Naples,Italy Ferritinophagy and Cell Cycle Control

SamiraLakhal-Littleton,DPhil University of Oxford Oxford,United Kingdom Ferroportin Mediated Control of Iron Metabolism and Disease

MitchellKnutson,PhD University of Florida Gainesville,FL Non-Transferrin-Mediated Iron Delivery

Emerging Biology Leading to New Therapies in Follicular Lymphoma

Dr. Pasqualucci will introduce general concepts about the cell of origin in follicular lymphoma and the mechanisms associated with clonal evolution. She will then examine the genetic events that take place early in the history of the tumor clone and focus on the role of histone/chromatin modifier genes, including the methyltransferase KMT2D and the acetyltransferases CREBBP/EP300, in the stepwise progression of the disease from a subclinical state to a pathological entity.

Dr. Fitzgibbon will provide an introduction to genomic discovery in follicular lymphoma. He will review the next generation sequencing tools that are being used to identify genetic predisposition factors and to perform molecular profiling to identify signaling mutations that may be targeted therapeutically and which provide insights into disease prognosis.

Dr. Smith will focus her discussion on emerging new treatment approaches for follicular lymphoma based on the novel concepts and new targets described by Drs. Nadel and Fitzgibbon. She will focus on the disease heterogeneity and prognosis, the clinical unmet needs, and how clinical integration of the new molecular tools is leading to an evolution in the therapeutic regimens for patients with follicular lymphoma.

Please click here to review this session.

WendyStock,MD The University of Chicago Chicago,IL

LauraPasqualucci,MD Columbia University New York City,NY Genetic-Driven Disruption of Epigenetic Circuits As Early Steps In The Pathogenesis Of Follicular Lymphoma

JudeFitzgibbon,PhD Queen Mary University of London London,United Kingdom Genomic Discovery, Prognosis, and Target Therapy Development

Sonali M.Smith,MD The University of Chicago Medicine Chicago,IL Follicular Lymphoma Therapy Based on Biological Insights and Novel Concepts

Focusing on Myeloid Neoplasia Through Splicing

Dr. Krainer will update the audience on the spliceosoma complex and splicing machinery. He will discuss functional implications in normal and pathological conditions.

Dr. Halene will focus on the pathogenetic mechanisms underlying specific mutations in MDS.

Dr. Walter will discuss the clinical implications of spliceosome gene mutations in MDS, their distribution in diverse subgroups and their prognostic significance. He will explore novel therapeutic approachesbased on use of drugs that modulate splicing to treat spliceosome mutant MDS.

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CristinaMecucci,MD, PhD University of Perugia Perugia,Italy

AdrianKrainer,PhD Cold Spring Harbor Laboratory Cold Spring Harbor,NY Spliceosome: Physiology and Disease Pathogenesis

StephanieHalene,MD, PhD Yale University School of Medicine New Haven,CT Functional Consequences of Spliceosome Mutations

Matthew J.Walter,MD Washington University in St. Louis St. Louis,MO Clinical Implications of Spliceosome Mutations: Epidemiology, Clonal Hematopoiesis, and Potential Therapeutic Strategies

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2016 Scientific Program

Sunday 2:00 pm - 8:00 pm Arrival and Check-in 6:00 pm Dinner 7:30 pm - 7:40 pm Welcome / Introductory Comments by GRC Site Staff 7:40 pm - 9:30 pm Keynote Session: Signaling Unity Within Epithelial Stem Cell Diversity Discussion Leader: Allan Spradling (Carnegie Institution for Science / Howard Hughes Medical Institute, USA) 7:40 pm - 7:50 pm Opening Remarks 7:50 pm - 7:55 pm Introduction by Discussion Leader 7:55 pm - 8:35 pm Roeland Nusse (Stanford University, USA) "Stem Cells in Liver Homeostasis" 8:35 pm - 8:45 pm Discussion 8:45 pm - 9:25 pm Fiona Watt (King's College London, United Kingdom) "In Vitro Approaches to Analyze the Epidermal Stem Cell Niche" 9:25 pm - 9:30 pm Discussion Monday 7:30 am - 8:30 am Breakfast 9:00 am - 12:30 pm Epithelial Stem Cells and Their Skin Niches Discussion Leaders: Fiona Watt (King's College London, United Kingdom) and Xiaoyang Wu (University of Chicago, USA) 9:00 am - 9:05 am Introduction by Discussion Leader 9:05 am - 9:25 am Howard Chang (Stanford University, USA) "RNA World and Regulation of Gene Expression" 9:25 am - 9:35 am Discussion 9:35 am - 9:55 am Pritinder Kaur (Curtin University, Australia) "MSC-Like Dermal Pericytes Influence Epidermal Renewal by Promoting Symmetric Keratinocyte Cell Divisions" 9:55 am - 10:00 am Discussion 10:00 am - 10:30 am Group Photo / Coffee Break 10:30 am - 10:50 am Valerie Horsley (Yale University, USA) "Adipocytes as Niche Cells in Epithelial Tissues" 10:50 am - 11:00 am Discussion 11:00 am - 11:20 am Xing Dai (University of California, Irvine, USA) "Keeping Skin and Mammary Epithelial Stem/Progenitor Cells Epithelial" 11:20 am - 11:30 am Discussion 11:30 am - 11:50 am Vladimir Botchkarev (Boston University, USA / University of Bradford, United Kingdom) "Epigenetic Regulation of Epidermal Development and Differentiation" 11:50 am - 12:00 pm Discussion 12:00 pm - 12:10 pm Aiko Sada (Tsukuba Advanced Research Alliance, University of Tsukuba, Japan) "Stem Cell Lineages of the Interfollicular Epidermis" 12:10 pm - 12:15 pm Discussion 12:15 pm - 12:25 pm Sangbum Park (Yale University, USA) "Coordination of Tissue Homeostasis and Wound Repair Mechanisms in Live Mice" 12:25 pm - 12:30 pm Discussion 12:30 pm Lunch 1:30 pm - 4:00 pm Free Time 3:00 pm - 4:00 pm Power Hour The GRC Power Hour is an optional informal gathering open to all meeting participants. It is designed to help address the challenges women face in science and support the professional growth of women in our communities by providing an open forum for discussion and mentoring. Organizers: Fiona Watt (King's College London, United Kingdom) and Jane Visvader (The Walter and Eliza Hall Institute of Medical Research, Australia) 4:00 pm - 6:00 pm Poster Session 6:00 pm Dinner 7:30 pm - 9:30 pm Epithelial Stem Cells in Translation Discussion Leaders: Michele De Luca (University of Modena and Reggio Emilia, Italy) and Andrea Flesken-Nikitin (Cornell University, USA) 7:30 pm - 7:55 pm Michele De Luca (University of Modena and Reggio Emilia, Italy) "Epidermal Stem-Mediated Combined Cell and Gene Therapy for the Treatment of Epidermolysis Bullosa" 7:55 pm - 8:05 pm Discussion 8:05 pm - 8:25 pm Graziella Pellegrini (University of Modena and Reggio Emilia, Italy) "Regenerative Medicine by Corneal Stem Cells: In Vitro and In Vivo Niches" 8:25 pm - 8:30 pm Discussion 8:30 pm - 8:50 pm Nadia Zakaria (Universitaire Ziekenhuis Antwerpen, Belgium) "Collagen Analogs as Scaffolds for Corneal Regeneration" 8:50 pm - 9:00 pm Discussion 9:00 pm - 9:10 pm Catherine Lu (The Rockefeller University, USA) "Identification of Adult Stem Cells in Eccrine Sweat Glands: Wound Repair and Regeneration" 9:10 pm - 9:15 pm Discussion 9:15 pm - 9:25 pm Clare Weeden (The Walter and Eliza Hall Institute of Medical Research, Australia) "Airway Basal Stem Cells Use Error-Prone DNA Repair in Response to DNA Damaging Agents" 9:25 pm - 9:30 pm Discussion Tuesday 7:30 am - 8:30 am Breakfast 9:00 am - 12:30 pm Hair Follicle Stem Cells Discussion Leaders: George Cotsarelis (University of Pennsylvania, USA) and Xinhong Lim (Institute of Medical Biology, A*STAR, Singapore) 9:00 am - 9:25 am George Cotsarelis (University of Pennsylvania, USA) "Bulge Stem Cells in Mouse and Human Hair Follicles" 9:25 am - 9:35 am Discussion 9:35 am - 9:55 am Sung-Jan Lin (National Taiwan University, Taiwan) "Environmental Regulation of Hair Follicle Neogenesis and Regeneration" 9:55 am - 10:00 am Discussion 10:00 am - 10:30 am Coffee Break 10:30 am - 10:50 am Tudorita Doina Tumbar (Cornell University, USA) "Genetic and Epigenetic Control of Stem Cell Dynamics in and out the Niche" 10:50 am - 11:00 am Discussion 11:00 am - 11:20 am Ting Chen (National Institute of Biological Sciences, China) "How to Build a Functional Niche with Stem Cells" 11:20 am - 11:30 am Discussion 11:30 am - 11:50 am Michael Rendl (Icahn School of Medicine at Mount Sinai, USA) "Regulation of Hair Follicle Formation, Growth and Regeneration by the Mesenchymal Niche" 11:50 am - 12:00 pm Discussion 12:00 pm - 12:10 pm Isaac Brownell (National Cancer Institute, NIH, USA) "The Perineural Niche as a Regulator of Cutaneous Stem Cells" 12:10 pm - 12:15 pm Discussion 12:15 pm - 12:25 pm Kenneth Lay (The Rockefeller University, USA) "Foxc1 Governs Hair Follicle Stem Cell Quiescence and Niche Maintenance to Preserve Long-Term Tissue-Regenerating Potential" 12:25 pm - 12:30 pm Discussion 12:30 pm Lunch 2:00 pm - 4:00 pm Poster Session 4:00 pm - 6:00 pm Lung Stem Cells Discussion Leaders: Brigid Hogan (Duke University, USA) and Nan Tang (National Institute of Biological Sciences, Beijing, China) 4:00 pm - 4:25 pm Brigid Hogan (Duke University, USA) "Lung Stem/Progenitor Cells and Their Niche During Homeostasis and Repair" 4:25 pm - 4:35 pm Discussion 4:35 pm - 4:55 pm Barry Stripp (Cedars Sinai Medical Center, USA) "Progenitor Cell Fate in Airway Repair" 4:55 pm - 5:05 pm Discussion 5:05 pm - 5:25 pm Joo-Hyeon Lee (University of Cambridge, United Kingdom) "Regulatory Crosstalk in Lineage Specification of Epithelial Cells During Lung Repair and Regeneration" 5:25 pm - 5:30 pm Discussion 5:30 pm - 5:40 pm Ian Driver (University of California, San Francisco, USA) "Single Cell Profiling of Adult Lung Heterogeneity: Identification of Novel Cell Types Involved in Regeneration and Disease" 5:40 pm - 5:45 pm Discussion 5:45 pm - 5:55 pm Rui Zhao (Genomics Institute of the Novartis Research Foundation, USA) "Tissue Logic in the Airway Epithelium: Plasticity and Regulation" 5:55 pm - 6:00 pm Discussion 6:00 pm Dinner Wednesday 7:30 am - 8:30 am Breakfast 9:00 am - 12:30 pm Intestinal Stem Cells Discussion Leaders: Bruce Edgar (Huntsman Cancer Institute, University of Utah Health Care, USA) and Zhengquan Yu (China Agricultural University, China) 9:00 am - 9:25 am Bruce Edgar (Huntsman Cancer Institute, University of Utah Health Care, USA) "Regenerative and Tumorigenic Growth of Drosophila Intestinal Stem Cells" 9:25 am - 9:35 am Discussion 9:35 am - 9:55 am Tony Ip (University of Massachusetts Medical School, USA) "The Conserved Misshapen-Yorkie Pathway in Drosophila Intestinal Homeostasis" 9:55 am - 10:05 am Discussion 10:05 am - 10:35 am Coffee Break 10:35 am - 10:55 am Heinrich Jasper (Buck Institute for Research on Aging, USA) "Age-Related Stem Cell Dysfunction: Lessons from Drosophila" 10:55 am - 11:05 am Discussion 11:05 am - 11:25 am Rongwen Xi (National Institute of Biological Sciences, China) "Fate Specification and Maintenance in the Midgut Stem Cell Lineages" 11:25 am - 11:35 am Discussion 11:35 am - 11:55 am Nozomi Nishimura (Cornell University, USA) "In Vivo Imaging of Stem Cells in the Mouse Intestine and Beyond" 11:55 am - 12:05 pm Discussion 12:05 pm - 12:25 pm Lucy O'Brien (Stanford University, USA) "Motile Stem Cells Exhibit Tissue-Level Spatial Order During Steady-State Organ Renewal but Not Adaptive Organ Growth" 12:25 pm - 12:30 pm Discussion 12:30 pm Lunch 1:30 pm - 4:00 pm Free Time 4:00 pm - 6:00 pm Poster Session 6:00 pm Dinner 7:00 pm - 7:30 pm Business Meeting Nominations for the Next Vice Chair; Fill in Conference Evaluation Forms; Discuss Future Site and Scheduling Preferences; Election of the Next Vice Chair 7:30 pm - 9:30 pm Epithelial Stem Cells of Oral and Craniofacial Complex Discussion Leaders: Ophir Klein (University of California, San Francisco, USA) and Tsung-Lin Yang (National Taiwan University, Taiwan) 7:30 pm - 7:50 pm Ophir Klein (University of California, San Francisco, USA) "Dynamics of Oral and Dental Epithelial Stem Cells During Homeostasis and Regeneration" 7:50 pm - 8:00 pm Discussion 8:00 pm - 8:20 pm Catherine Ovitt (University of Rochester, USA) "Finding a Role for Stem Cells in Salivary Gland Homeostasis" 8:20 pm - 8:30 pm Discussion 8:30 pm - 8:50 pm Yang Chai (University of Southern California, USA) "Molecular Regulation of the Dental Epithelial Stem Cell Niche" 8:50 pm - 9:00 pm Discussion 9:00 pm - 9:10 pm Maria Alcolea (Wellcome Trust/MRC Cambridge Stem Cell Institute, United Kingdom) "Cell Fate Imbalance in the Oesophageal Epithelium: Mutant Cell Competition" 9:10 pm - 9:15 pm Discussion 9:15 pm - 9:25 pm Sarah Knox (University of California, San Francisco, USA) "Peripheral Nerves Selectively Establish, Maintain and Replenish Salivary Gland Architecture via SOX2" 9:25 pm - 9:30 pm Discussion Thursday 7:30 am - 8:30 am Breakfast 9:00 am - 12:30 pm Mammary, Prostate, and Ovarian Stem Cells Discussion Leaders: Michael Shen (Columbia University Medical Center, USA) and Chang Liu (Columbia University, USA) 9:00 am - 9:25 am Michael Shen (Columbia University Medical Center, USA) "Progenitor Cells and the Origin of Prostate Cancer" 9:25 am - 9:35 am Discussion 9:35 am - 9:55 am Li Xin (Baylor College of Medicine, USA) "Prostate Epithelial Lineage Hierarchy" 9:55 am - 10:00 am Discussion 10:00 am - 10:30 am Coffee Break 10:30 am - 10:50 am Arial Zeng (Chinese Academy of Sciences, China) "Procr Stem Cells in Mammary Development and Cancer" 10:50 am - 11:00 am Discussion 11:00 am - 11:20 am Allan Spradling (Carnegie Institution for Science / Howard Hughes Medical Institute, USA) "Controlling the Onset of Epithelial Differentiation Downstream from the Stem Cell" 11:20 am - 11:30 am Discussion 11:30 am - 11:50 am Jane Visvader (The Walter and Eliza Hall Institute of Medical Research, Australia) "Mapping Stem and Progenitor Cells During Development and Tumorigenesis" 11:50 am - 12:00 pm Discussion 12:00 pm - 12:10 pm Qiang Lan (Institute of Biotechnology, University of Helsinki, Finland) "Cellular Behavior of Mammary Progenitor Cells During Embryonic Mammary Gland Development" 12:10 pm - 12:15 pm Discussion 12:15 pm - 12:25 pm Winnie Shum (ShanghaiTech University, China) "Epithelial Cellular Communication for a Congenial Niche in Excurrent Duct" 12:25 pm - 12:30 pm Discussion 12:30 pm Lunch 1:30 pm - 4:00 pm Free Time 4:00 pm - 6:00 pm Stem Cells of Transitional Zones Discussion Leaders: Alexander Nikitin (Cornell University, USA) and Guy Lyons (Centenary Institute, Australia) 4:00 pm - 4:25 pm Alexander Nikitin (Cornell University, USA) "Transitional Zones, Stem Cells and Cancer" 4:25 pm - 4:30 pm Discussion 4:30 pm - 4:50 pm Geraldine Guasch (Institut Paoli Calmettes, Cancer Research Center of Marseille, France) "Transitional Epithelium: Merging Microenvironment and Cellular Transformation" 4:50 pm - 4:55 pm Discussion 4:55 pm - 5:15 pm Yusuke Yamamoto (National Cancer Center Research Institute, Japan) "Enemies from Within: Stem Cells of Metaplastic Precursors of Highly Lethal Cancers" 5:15 pm - 5:20 pm Discussion 5:20 pm - 5:30 pm Joana Neves (Buck Institute for Research on Aging, USA) "Immune Modulation by MANF Promotes Tissue Repair and Regenerative Success in the Retina" 5:30 pm - 5:35 pm Discussion 5:35 pm - 5:45 pm Jeff Mumm (Johns Hopkins School of Medicine, USA) "Innate Immune System Regulation of Retinal Regeneration" 5:45 pm - 5:50 pm Discussion 5:50 pm - 6:00 pm Closing Remarks 6:00 pm Dinner Friday 7:30 am - 8:30 am Breakfast 9:00 am Departure

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Tissue Niches & Resident Stem Cells in Adult Epithelia - GRC