2008-12-08

The ASH Scholar Awards are highly competitive grants that provide partial salary support during the transitional period between completion of training and achievement of status as an independent investigator. The goal of the program is to encourage beginning hematologists to pursue a research career in either basic or clinical/translational research. ASH News Daily is proud to feature profiles of some of the current class of scholars in each issue of the paper at this year’s annual meeting.

Akil Merchant, MD, a Basic Research Fellow Scholar, is a medical oncology fellow at Johns Hopkins University, where he studies the hedgehog signaling pathway in normal and malignant hematopoiesis. Dr. Merchant’s previous work, in the laboratory of Margaret Goodell, focused on understanding the genetic programs regulating hematopoietic stem cells and their responses to chemotherapy. His current work builds on these insights to explore how dysregulation of normal developmental pathways critical for hematopoiesis lead to cancer and chemoresistance. With his current mentor, Bill Matsui, he has demonstrated that hedgehog signaling is critical for myeloid development, is activated in the majority of acute myeloid leukemias, and is up-regulated in leukemia cancer stem cells. His project is to better understand the clinical consequences of hedgehog pathway activation in leukemia and cancer stem cells and explore the role of hedgehog pathway inhibitors as new therapies for hematologic diseases. 

At the conclusion of his fellowship, Dr. Merchant plans a career as a laboratory-based translational researcher in hematologic malignancies. He hopes to continue studying cancer stem cells, their interactions with their niche and tumor microenvironment, and their mechanisms of self-renewal and chemoresistance in order to better develop new therapies that can eliminate these cells and improve cancer cure rates. 

David Motto, MD, PhD, a Basic Research Junior Faculty Scholar, is an assistant professor of internal medicine and pediatrics at the University of Iowa. Dr. Motto received his MD and PhD degrees from the University of Iowa and completed his clinical training in pediatrics and pediatric hematology/oncology at the University of Michigan. Dr. Motto’s laboratory studies the biochemistry, physiology, and genetics of blood clotting diseases and platelet biology. He is currently focusing on the thrombotic microangiopathies (TMAs), which are characterized clinically by small blood vessel thrombosis of various organs, coupled with thrombocytopenia and the physical destruction of red blood cells. The two most common TMAs are thrombotic thrombocytopenic purpura (TTP) and the closely related hemolytic-uremic syndrome (HUS). Dr. Motto is investigating potential shared mechanisms of pathogenesis between TTP and HUS.

Charles Mullighan, MD, Basic Research Fellow Scholar, received his undergraduate medical training and specialist training in hematology and hematopathology in Adelaide, Australia, and undertook doctoral work in immune response genetics in Oxford, UK. Since 2004, he has been a postdoctoral fellow in the laboratory of Dr. James Downing, scientific director at St. Jude Children’s Research Hospital. His research interests are using genomic approaches to identify genetic alterations contributing to leukemogenesis, and modeling of leukemogenic mutations in experimental systems. His recent work has identified a high frequency of novel genetic alterations in acute lymphoblastic leukemia, most notably involving genes encoding regulators of B-lymphoid development in B-progenitor ALL (Nature 2007;446:758). Recent work has identified a near obligate deletion of Ikaros (IKZF1) in BCR-ABL1 lymphoid leukemia, including de novo BCR-ABL1 ALL and CML in lymphoid blast crisis (Nature 2008;453:110). His current work continues to use cutting-edge genomic approaches to identify the full complement of genomic abnormalities contributing to leukemogenesis, treatment resistance, and relapse, including profiling of copy number alterations, gene expression, and methylation, and high-throughput/next-generation sequencing approaches. His work also uses knockout and retroviral bone marrow transplant models of acute lymphoblastic leukemia to examine the role of individual mutations in leukemogenesis.

Eric S. Mullins, MD, a Basic Research Fellow Scholar, is a pediatric hematologist at Cincinnati Children’s Hospital Medical Center with a clinical interest in hemostasis and thrombosis. His undergraduate and medical degrees were awarded by the University of Missouri, followed by residency at Vanderbilt Children’s Hospital. Dr. Mullins completed his fellowship at Cincinnati Children’s Hospital, during which he received the National Hemophilia Foundation Clinical Fellow Award and served as chief fellow. In the laboratory of Dr. Jay L. Degen, Dr. Mullins began an investigation into the role of thrombin in the maintenance of vascular integrity, development, and inflammation. This work led to the ASH Scholar Award to further this investigation of the role of thrombin and thrombin targets in asthmatic disease in mice. Previous studies implicated both activated thrombin and fibrin in the pathogenesis of asthma, but the precise contribution of these hemostatic factors to the disease has not been characterized. His work focuses on using existing and novel transgenic mice to define the contribution of coagulation proteins to asthmatic disease. He has also begun an exciting new investigation into the role of thrombin-mediated proteolysis in experimental autoimmune encephalitis, with strong evidence pointing to the critical role of thrombin in exacerbation of this disease process.

Cindy N. Roy, PhD, a Basic Research Junior Faculty Scholar, received her PhD in cell biology from Oregon Health Sciences University. Guided by Caroline Enns, PhD, she investigated the role of the hereditary hemochromatosis gene product, HFE, in the regulation of transferrin-mediated cellular iron uptake. Dr. Roy was mentored through her postdoctoral fellowship in hematology by Nancy Andrews, MD, PhD, at Harvard Medical School/Children’s Hospital Boston. There, she investigated the role of hepcidin antimicrobial peptide in the pathogenesis of anemia associated with inflammation and gained expertise in the development of animal models of human disease. Dr. Roy has recently joined the faculty of the Biology of Frailty Program in the Division of Geriatric Medicine and Gerontology at Johns Hopkins University School of Medicine, where she aims to develop novel strategies and tools for the diagnosis, treatment, and prevention of anemia in the elderly. Currently, her laboratory is working toward a molecular understanding of how the immune response modulates genes and gene products required for erythrocyte iron recycling and the production and maturation of erythroid progenitors. Dr. Roy would like to thank Drs. Enns, Andrews, and Walston; ASH; and ASH’s corporate supporters for their commitment to her personal and professional development.

Joshua D. Schiffman, MD, a Clinical/Translational Research Fellow Scholar, is focusing on the predisposition to and genetic alterations of childhood cancers, with an emphasis on leukemia. He recently began a translational research position as an assistant professor in Pediatric Hematology/Oncology at Primary Children’s Medical Center, and he is an adjunct investigator in the Department of Oncological Sciences at the University of Utah’s School of Medicine and the Huntsman Cancer Institute in Salt Lake City. Additionally, he is the medical director of the High Risk Pediatric Cancer Clinic; the clinic cares for children and families with hereditary cancer syndromes. Previously, he completed his fellowship training at Stanford University School of Medicine. This was followed by a year of working in Dr. James Ford’s laboratory and serving as co-director of the Pediatric Cancer Genetics Clinic at Stanford. Under Dr. Ford’s mentorship, Dr. Schiffman learned how to acquire clinical samples from high-risk patients with cancer predisposition syndromes and perform genomic analyses to better understand cancer etiology and clinical outcome. Dr. Schiffman is grateful to be an ASH Scholar.

Matthew P. Strout, MD, PhD, a Basic Research Fellow Scholar, is an associate research scientist and staff physician in the Department of Internal Medicine, Section of Hematology, and an instructor in the Department of Molecular Biophysics and Biochemistry at Yale University School of Medicine. Dr. Strout earned his PhD in molecular immunology from the Roswell Park Cancer Institute where, under the mentorship of Dr. Michael Caligiuri, he co-discovered and characterized the partial tandem duplication of the MLL gene in acute myeloid leukemia. After earning his MD from The Ohio State University, Dr. Strout moved to Yale University where he completed a residency in internal medicine and a fellowship in hematology. Dr. Strout is now working in the laboratory of Dr. David Schatz studying the role of immune diversification in the development of lymphoid malignancy. He is specifically interested in understanding the mechanisms that maintain genomic stability during somatic hypermutation and how those mechanisms break down during malignant transformation. Dr. Strout is board-certified in internal medicine and hematology and attends on the hematologic malignancy service at Yale-New Haven Hospital. In addition to his support from ASH, Dr. Strout has received awards from the Lady Tata International Trust for Leukemia Research and the Leukemia and Lymphoma Society.

Geoffrey Uy, MD, a Clinical/Translational Research Fellow Scholar, is interested in the development of new agents and treatment approaches for patients with myelodysplastic syndromes and acute myeloid leukemia. After completing his fellowship in hematology/oncology at Washington University, he joined the faculty as an assistant professor of medicine in the Section of BMT & Leukemia. During his fellowship, Dr. Uy trained in the lab of Timothy J. Ley, MD, where he has investigated the role of proteolytic cleavage of PML-RAR in the pathogenesis of acute promyelocytic leukemia. In conjunction with Dr. John DiPersio, they are currently conducting a phase I/II study of AMD3100 (plerixafor) in combination with mitoxantrone, etoposide, and cytarabine for relapsed or refractory AML. AMD3100 is a CXCR4 antagonist currently under clinical development as a stem cell mobilizing agent for use in hematopoietic transplantation. Preclinical evidence suggests that AMD3100 can disrupt the interaction of leukemic blasts with the bone marrow microenvironment, sensitizing these cells to genotoxic stresses such as chemotherapy. This trial is designed as a proof-of-concept study to determine if AMD3100 "priming" can be safely administered and whether it can improve response rates in AML. 

Loren D. Walensky, MD, PhD, a Basic Research Junior Faculty Scholar, is an assistant professor of pediatrics at Harvard Medical School, medical director of the Dana-Farber Cancer Institute’s Program in Cancer Chemical Biology, and attending physician in the Department of Pediatric Hematology/Oncology at Dana-Farber/Children’s Hospital Boston. His laboratory’s research focuses on the chemical biology of deregulated apoptotic and transcriptional pathways in cancer, with the goal of developing an arsenal of new compounds — a "chemical toolbox"— to investigate and modulate protein interactions that cause cancer. His laboratory takes a multidisciplinary approach that employs synthetic chemistry techniques; structural biology analyses; and biochemical, cellular, and mouse modeling experiments to systematically dissect the pathologic signaling pathways of interest. Dr. Walensky received his MD and PhD degrees from the Johns Hopkins University School of Medicine, completing his graduate training in the laboratory of Solomon H. Snyder, MD. He trained in pediatrics at the Boston Combined Residency Program in Pediatrics and completed his fellowship training in pediatric hematology/oncology at Dana-Farber/Children’s Hospital Boston. His postdoctoral fellowship research, which led to the development of pro-apoptotic "stapled" peptides, was jointly mentored by Stanley J. Korsmeyer, MD, of Dana-Farber and Gregory L. Verdine, PhD, of Harvard University. Dr. Walensky’s ASH-sponsored research program involves the creation of new technologies to dissect the molecular mechanism of BAX-mediated apoptosis, with a keen eye toward clinical application.

Zack Z. Wang, PhD, a Basic Research Junior Faculty Scholar, is a principal investigator at Maine Medical Center Research Institute (MMCRI) and the Center for Molecular Medicine, and received his PhD at Boston University School of Medicine in the Department of Biochemistry in 1998. His thesis research in Katya Ravid’s laboratory involved the study of molecular hematopoiesis, focusing on the mechanisms of cell cycle regulation of polyploidy in megakaryocytes, the platelet precursors. He did his postdoctoral training in the laboratory of Dr. David Scadden in the Center of Regenerative Medicine at Massachusetts General Hospital and Harvard Stem Cell Institute, where he investigated hematopoietic and blood vessel development. His study demonstrated that tyrosine kinase receptor EphB4 plays a crucial role in regulating hemangioblast development. After leaving an instructor position at Harvard Medical School, he joined MMCRI in 2005 to establish his independent laboratory and direct the ES cell core facility. His laboratory focuses on defining the factors that direct pluripotent stem cell differentiation into hematopoietic and cardiovascular cells.

David C. Williams Jr., MD, PhD, a Basic Research Junior Faculty Scholar, completed a Medical Scientist Training Program at the University of Virginia in 1998 where he earned a PhD in Biophysics and an MD. His residency training was in anatomic pathology at Duke University, where Dr. Williams developed an interest in hematopathology. He spent four years as a postdoctoral fellow at the National Institutes of Health pursuing structural biology research with G. Marius Clore, MD, PhD. After that exciting experience, Dr. Williams decided to finish his clinical training with a hematopathology fellowship at Virginia Commonwealth University and then pursued an academic research career. Currently, he is an assistant professor in the Pathology Department at Virginia Commonwealth University, spending most of his time running a research laboratory focused on the structural biology of transcription factor complexes important for globin gene regulation and leukemogenesis. His clinical responsibilities primarily involve performing and interpreting bone marrow biopsies for a very active clinical service. While Dr. Williams’s clinical and research expertise appear to be quite disparate, both appeal to his interest in structure-function relationships.Ultimately, his goal is to use his basic science skills to help develop biologically targeted therapy for hematopoietic diseases.

Jing Yang, PhD, a Clinical/Translational Research Fellow Scholar, works in the Department of Lymphoma and Myeloma at the University of Texas, M. D. Anderson Cancer Center. She obtained her PhD in 2002 from Cancer Research Institute, Xiangya Medical College, at Central South University in China. In 2004, Dr. Yang joined the Myeloma Institute for Research and Therapy at the University of Arkansas for Medical Sciences as a postdoctoral fellow. A half-year later, she was recruited to M. D. Anderson Cancer Center. Her specific concentration in translational research is to explore the ability of monoclonal antibodies (mAbs) against human b2-microglobulin (b2M) to induce apoptosis in myeloma and elucidate the underlying mechanism. Currently, Dr. Yang is successfully generating her own mAbs, evaluating tumoricidal effects of the mAbs to treat myeloma and other hematologic malignancies and the established tumors in SCID mice, elucidating apoptosis and signaling pathways in tumor cells, and examining the potential toxicity of the mAbs on normal cells. Her studies provide strong evidence for the future application of anti-b2M mAbs as therapeutic agents for myeloma and other hematologic malignancies.

Chengcheng (Alec) Zhang, PhD, a Basic Research Junior Faculty Scholar, earned his bachelor’s degree at the University of Science and Technology of China and his master’s at the Chinese Academy of Sciences. From 1995 to 1999, he pursued his PhD in biochemistry from the University of Illinois at Urbana-Champaign, studying estrogen-receptor-mediated transcriptional regulation and signal transduction. In 2000, he went on to perform postdoctoral work with Harvey Lodish at the Whitehead Institute for Biomedical Research, with fellowship support from the Leukemia and Lymphoma Society. There he developed his interest in identification of novel growth factors and markers for hematopoietic stem cells and establishment of an ex vivo culture system for expanding these cells. Dr. Zhang joined UT Southwestern Medical Center as an assistant professor in the Departments of Physiology and Developmental Biology in January 2007. He is studying the extrinsic control of cell fates of hematopoietic stem cells, leukemia stem cells, and the interplay between hematopoietic stem cells, microenvironment, and cancer. His goal is to seek a comprehensive understanding of the molecular mechanisms governing the adult stem cell fate determination and applying the knowledge obtained from these studies to the development of new stem cell transplantation strategies and gene therapies for treating cancer and other diseases.

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