Joshua J. Field, M.D. was the first scholar in the K12 Clinical Hematology Research Career Development Program at Washington University. He was an Assistant Professor in the Division of Hematology of the Department of Medicine. Josh received a Master of Science degree in Genetic Epidemiology through the GEMS program. His area of research was clinical investigation of adults with sickle cell disease. In collaboration with senior investigators, he had several clinic studies open that focus on elucidating the mechanisms of cardiac and pulmonary complications among adults with sickle cell disease with the long-term goal of identifying potential therapeutic targets. On July 1, 2010 Josh assumed duties as Associate Medical Director at the Blood Center of Wisconsin and Assistant Professor of Medicine at the Medical College of Wisconsin. Dr. Field specializes in the treatment of sickle cell disease and other benign hematological disorders at Froedtert Hospital and the Children's Hospital of Wisconsin.
Coy D. Heldermon, M.D., Ph.D. was the second scholar in the K12 Clinical Hematology Research Career Development Program at Washington University. He was an Instructor in the Division of Oncology of the Department of Medicine, working in the laboratory of Mark Sands, Ph.D. where he researched therapy of inherited disorders with gene replacement and in utero stem cell approaches.
Dr. Heldermon accepted a tenure-track Assistant Professorship at the University of Florida School of Medicine in Gainesville, Florida, beginning July 1, 2009. His research expertise is in the use of gene replacement and stem cell therapies for the treatment of inherited disorders such as lysosomal storage diseases. He also studies the spread of stem cells from maternal or malignant sources using mouse models.
Ghada, M. Kunter, M.D. was a member of the third class of scholars in the K12 Clinical Hematology Research Career Development Program at Washington University. Dr. Kunter's research interest primarily focuses on studying the molecular basis of severe congenital neutropenia (SCN) an inherited bone marrow failure syndrome with a marked predisposition to transform to myelodysplasia (MDS) and myeloid leukemia (AML). The molecular mechanisms contributing to transformation in SCN are largely unknown, limiting progress in this syndrome.The prognosis of patients with SCN who transform to MDS/AML is devastating. Consequently, there is a pressing need to identify patients at risk for transformation and develop strategies for prevention and targeted therapies. Dr. Kunter will begin a fellowship program at Emory University in Atlanta, GA on July 1, 2013.
Mark A. Schroeder, M.D. was a member of the third class of scholars in the K12 Clinical Hematology Research Career Development Program at Washington University. Dr. Schroeder's research interest is in the pathophysiology of myelodysplastic syndromes (MDS) and key alterations in the bone marrow microenvironment occurring in this disease. His clinical interests include MDS and its treatment by hematopoietic stem cell transplantation and novel treatment approaches. His clinical research project will use novel drugs to disrupt dysplastic blasts from the protective bone marrow niche and sensitize them to the effects of hypomethylating agents. This trial and its correlative studies will help to better understand the progression, and treatment of MDS. Dr. Schroeder was recently awarded a Masters of Science degree in Clinical Investigation in the CRTC program. He was promoted to Assistant Professor of Medicine at Washington University School of Medicine in 2012 and continues his work in the laboratory of Dr. John DiPersio.
Meagan A. Jacoby, M.D., Ph.D. was a member of the fourth class of scholars in the K12 Clinical Hematology Research Career Development Program at Washington University. Dr. Jacoby's research interest focuses on the role of the DNA damage response and DNA repair in the pathogenesis of myelodysplastic syndromes (MDS). Dr. Jacoby is studying the DNA damage response and ability to repair DNA damage in primary samples from MDS patients. The goal of this research is not only to better understand disease pathogenesis, but to determine if DNA damage response defects can be exploited therapeutically to provide novel agents for the treatment of MDS.
Stephen T. Oh, M.D., Ph.D. was a member of the fourth class of scholars in the K12 Clinical Hematology Research Career Development Program at Washington University. Dr. Oh's primary research interest is mechanisms of dysregulated signaling in myeloproliferative neoplasms (MPNs). Dr. Oh and his colleagues recently discovered novel mutations in the adapter protein LNK, a negative regulator of JAK-STAT signaling, in patients with MPNs, and ongoing work is aimed at characterizing the functional impact of these LNK mutations on MPN pathogenesis. Dr. Oh utilizes phospho-specific flow cytometry to directly evaluate signaling in MPN patient samples, and is applying next-generation mass cytometry technologies to characterize aberrant signaling at the network level. The ultimate goal is to translate this work into improved therapies for MPN patients. Dr. Oh is currently an Assistant Professor in the Division of Hematology, Department of Medicine at Washington University School of Medicine.
Kristin Sanfilippo, M.D. is a member of the fifth class of scholars in the K12 Clinical Hematology Research Career Development Program at Washington University. Kristen is in her final year of hematology/oncology fellowship. She received a Master of Population Health Science (MPHS) during her second year of fellowship. Her area of research interest is focused on health outcomes and risk prediction in patients with hematologic disorders. She is preparing to participate in ASH CRTI to solidify her research plan to predict risk of venous thromboembolism in patients with multiple myeloma. This model can be modified for translation to additional high risk patient populations as well as be incorporated in future clinical trials comparing the effectiveness of primary thromboprophylaxis in prevention of venous thromboembolism in patients identified as highest risk.
Eric Duncavage, M.D. is a member of the sixth class of scholars in the K12 Clinical Hematology Research Career Development Program at Washington University. Eric is an assistant professor in the Division of Anatomic and Molecular Pathology where his primary clinical responsibilities include diagnostic hematopathology and molecular oncology. Eric's research interest is in the molecular pathogenesis and diagnosis of myelodysplastic syndromes (MDS), which affect over 10,000 new patients annually. Recent studies have shown that recurrent genetic mutations in a core set of genes are present in the majority of MDS patients. Identification of these mutations can simplify diagnosis and in many cases is associated with distinct clinical outcomes. Eric's current research project involves the development of 'ultra-sensitive' next generation sequencing methods for the identification of small clonal populations in MDS. The presence of these small clonal populations has the potential to make more accurate diagnoses and better monitor MDS patients for recurrence and transformation.
Melanie Fields, M.D. joined the HemeScholars in June 2014. Melanie is in her final year of pediatric hematology/oncology fellowship, and is currently completing her thesis for her Masters of Science in Clinical Investigation at Washington University. Her research focuses on improving our understanding of the pathophysiology of stroke, specifically silent cerebral infarcts, in sickle cell disease through neuroimaging. Silent cerebral infarcts are a common cause of morbidity secondary to their association with cognitive deficits in patients with sickle cell disease. She utilizes MR measurements of cerebral blood flow and oxygen extraction fraction to better understand the mechanisms of these lesions, with the long-term goal of developing a screening tool and identifying primary preventive therapies.
Terrence Wong, M.D., Ph.D. will join the K12 HemeScholars Program in June 2015. Terrence is in the final year of his clinical fellowship in the Division of Hematology/Oncology at Washington University. His research focuses on how cytotoxic therapy influences the clonal dynamics of hematopoietic populations. Recent studies have revealed that hematopoietic stem cells (HSCs) acquire somatic mutations with age, and that each individual possesses a genetically heterogeneous hematopoietic population. Previously, Dr. Wong and his colleagues identified small populations of hematopoietic cells harboring deleterious TP53 mutations in a significant fraction of individuals with morphologically normal hematopoiesis never exposed to cytotoxic therapy. Exposure of individuals possessing hematopoietic populations with somatic TP53 (or other) mutations to cytotoxic therapy may predispose them to the future development of therapy-related hematologic disease. By understanding how cytotoxic therapy influences genetically heterogenous hematopoietic populations, we can potentially abrogate the long-term effects of chemotherapy and radiation.
Chang Liu, M.D., Ph.D. joined the K12 HemeScholars Program in June 2016. Chang is an assistant professor in the Division of Laboratory and Genomic Medicine, Department of Pathology and Immunology. He was trained in Clinical Pathology, Transfusion Medicine, and Histocompatibility at Barnes-Jewish Hospital/Washington University. He is currently an attending physician on the Transfusion service and will be the Director of HLA laboratory in July 2016. Chang's research interest is the application of next-generation sequencing (NGS) in HLA typing and the genetics of immune-related hematological diseases such as heparin-induced thrombocytopenia (HIT). The long-term goal is to harness the power of NGS technology to achieve fast, and haplotype-resolved HLA typing to benefit transplant patients, and to identify genetic markers for risk stratification of patients susceptible to HIT and other immune-related disorders.
Principal Investigator/Program Director
J. Evan Sadler, M.D., Ph.D. is Professor of Medicine and Biochemistry & Molecular Biophysics, Chief of the Division of Hematology and the Ira M. Lang Endowed Chair for The Foundation for Barnes-Jewish Hospital. Dr. Sadler is responsible for all aspects of the program. In particular, he coordinates meetings of the Advisory Committee, participates in Scholar recruitment, oversees the review of applications to the Program, matches Scholars with Mentors, meets regularly with Scholars and Mentors, reviews annual Scholar progress reports, and teaches in the clinical core curriculum.
Susie Hahn takes care of day-to-day program administration, coordinates the Scholar recruitment and application processes, and generally keeps everything running.
The Advisory Committee provides general oversight of the Program, serves as a study section to review Scholar applications, monitors Scholars' progress, and provides an annual report of the Program's development, strengths and weaknesses, and recommendations for improvement. The Advisory Committee members were selected for their exceptional multidisciplinary expertise in clinical research and training, qualities that are congruent with the Program's career development and clinical research focus.
Alan L. Schwartz, M.D., Ph.D., is the Chair of the K12 Advisory Committee. Dr. Schwarz also is Chairman of Pediatrics and Pediatrician-in-Chief at SLCH. He will contribute his extensive experience in non-malignant hematology research, in organizing clinical and research training programs, and in mentoring of physician-scientists. Dr. Schwartz' major research interest is the cell and molecular biology of receptor-mediated endocytosis. He has published extensively on aspects of cellular, molecular and developmental biology, and has been funded continuously by the NIH since 1979. Dr. Schwartz received the E. Mead Johnson Award for clinical and laboratory research achievements from the Society for Pediatric Research in 1993. He is a member of the Institute of Medicine of the National Academy of Sciences. He has had administrative responsibilities as Director of the Division of Hematology-Oncology (1986-1995) where he established and directed (1991-1998) the Lucille P. Markey Special Emphasis Pathway in Human Pathobiology. He has served as Chairman of the Department of Pediatrics since 1995. Dr. Schwartz serves as the Principal Investigator if the NICHD-funded Child Health Research Center. Dr. Schwartz has trained many national leaders in pediatric hematology, including Michael DeBaun, a leader in clinical research in sickle cell disease, an outstanding mentor and member of our Program Faculty.
Bradley Evanoff, M.D., M.P.H., is Professor of Internal Medicine and Director of the Division of General Medical Sciences. He is also Director of the Institute of Clinical and Translational Sciences and the Assistant Dean for Clinical and Translational Research. Dr. Evanoff brings to the Program his experience in developing and implementing a comprehensive curriculum to train clinical researchers. Dr. Evanoff is the Principal Investigator on the K30 Clinical Research Curriculum Award that supports the Core Curriculum in Clinical Investigation (CCCI) and the degree-granting Mentored Training Program in Clinical Investigation (MTPCI) at Washington University. Dr. Evanoff completed a fellowship in epidemiology at the Karolinska Hospital in Stockholm, and pursued further training in clinical research design in the Robert Wood Johnson Clinical Scholars Program. He has established a nationally recognized research program focused on the epidemiology of occupational injuries and musculoskeletal disorders. He has been the Principal Investigator of R01 grants, a K07 Curriculum development award, and other grants. He has served on NIH and CDC study sections, and is a member of the Occupational Safety and Health study section. Under his K07 award, Dr. Evanoff established teaching in occupational and environmental health, epidemiology, and preventive medicine for medical students and residents. Students of the Medical School have recognized his abilities as a teacher and coursemaster by twice voting him a Distinguished Service Teaching Award (1997 and 2003) and Lecturer of the Year (1998 and 2001). Since assuming the role of Division Chief in 1998, Dr. Evanoff has overseen a large increase in the external research funding of faculty in his Division, has mentored faculty members in the Division to promotion with tenure, and has guided junior faculty members in successful applications for career development awards. Dr. Evanoff has mentored fellows through research opportunities in the Division of GMS and through other Divisions and Departments. He also serves as a faculty research mentor to students in the Doris Duke Clinical Research Fellowship program.
Victoria J. Fraser, M.D., is the Adolphus Busch Professor and Chairman of the Department of Internal Medicine. Dr. Fraser is the first recipient of the William Campbell Endowed Chair for Excellence in Clinical Infectious Disease. She is the recipient of the Society for Healthcare Epidemiology's Young Investigator Award, the Neville Grant Award for Clinical Excellence, the Bi-State Public Health Award, and the Mentoring Award from the Academic Women's Network. She has successfully developed and led multidisciplinary teams at WUMC and BJC HealthCare including chairing the committee on improving the recruitment, retention and promotion of women and minorities; leading the BJC HealthCare Infection Control Consortium (in integrated network of infection control programs from 13 hospitals); and developing the Helena Hatch Special Care Center for Women with HIV (a multidisciplinary health care delivery system for women and children with HIV. She has an international reputation for her work in health care epidemiology particularly studying adverse events in health care, both in patients and health care workers, and developing and implementing interventions to improve health care delivery. She has had investigator-initiated grant support from CDC, HRSA, and AHRQ since 1993. She has served on CDC and NIH study sections and on HRSA, AHRQ and CDC steering committees. Dr. Fraser is the Chair of Washington University's Department of Medicine Committee on Junior Faculty Recruitment and Retention with the goal of promoting the recruitment and retention of women in academic medicine. In addition, she is the Principal Investigator on the NIH-funded K12 Multidisciplinary Clinical Research Career Development Program at WUMC, which has a structure and goals similar to the more focused Heme Scholars program. Her experience and ability in performing clinical research, mentoring clinical researchers, and directing a clinical research career development program are perfectly suited to her role on the Advisory Committee.
John C. Morris, M.D., is the Harvey and Dorismae Hacker Friedman Distinguished Professor of Neurology, Professor of Pathology and Immunology, and Professor of Physical Therapy. His knowledge and experience in the performance of multidisciplinary clinical research, and in clinical research training, is invaluable to the Heme Scholars program. The focus of Dr. Morris' research and practice is Alzheimer's disease and other neurological disorders associated with aging. Dr. Morris is the Director and Principal Investigator of the Alzheimer's Disease Research Center. He is the Principal Investigator of the program project, "Healthy Aging and Senile Dementia," another program project, "Antecedent Biomarkers for AD-The Adult Children Study", and the center grant, "Alzheimer Disease Research Center," all funded by the National Institute on Aging (NIA). He is the recipient of an academic leadership award from the NIA to establish Washington University's Center for Aging, which he directs. He also directs the Memory Diagnostic Center at BJH and the Memory and Aging Project at WUMC. Dr. Morris is author or co-author of over 200 peer-reviewed journal articles and 50 chapters and reviews. He has received many honors, including the Distinguished Achievement Citation (2000) from his alma mater, Ohio Wesleyan University, The Lifetime Achievement Award (2004) from the National Alzheimer's Association, the 2004 MetLife Foundation Award for Medical Research, and the 2005 Potamkin Prize for Research in Pick's, Alzheimer's, and Related Disease from the American Academy of Neurology. Dr. Morris serves the Medical School as Coursemaster for several electives focusing on aging and dementia. He has mentored many academic clinical researchers.
Clinical Research Teams
Mentors are organized into three teams that represent major areas of expertise in non-malignant clinical research at WUMC (Table). This structure is not meant to be rigid, but is intended to facilitate discussion. We could describe the traditional strengths of our research in other ways, and we naturally will conduct clinical research that falls outside of these neat categories. Similarly, the lists of Mentors are for illustration and are not exhaustive.
Mentors come from many departments and occupy a variety of niches in the clinical research enterprise. Some are molecularly oriented, with strong records in the study of disease mechanisms and translational research. Others perform patient oriented clinical research, and others are superb clinicians with well-established patient populations affected by hematologic diseases. Some of us can and will contribute to more than one team. For example, based on their knowledge and experience, Drs. Blinder, Ley and Shenoy are shown as belonging to two teams. Diane Merritt investigates menorrhagia and is listed under Hemostatic and Thrombotic Disorders, but may contribute to any project relevant to women's health.
|Table of Clinical Research Teams
|Hematopoietic Stem Cell and|
|Kenneth R. Carson||John P. Atkinson||Morey A. Blinder
|Mary C. Dinauer||Morey A. Blinder||Charles S. Eby
|John F. DiPersio||George J. Broze||Brenda J. Grossman|
|Timothy J. Ley||Charles S. Eby||Monica L. Hulbert|
|Daniel C. Link||Brian F. Gage||Allison A. King||Rob D. Mitra||Elaine M. Majerus||Jin-Moo Lee
||Mark S. Sands||Diane F. Merritt||Timothy J. Ley
||Shalini Shenoy||J. Evan Sadler||Elaine M. Majerus
||Matthew J. Walter||Douglas M. Tollefsen||Philip C. Spinella
||David B. Wilson||David B. Wilson||Shalini Shenoy
Hematopoietic Stem Cell and Leukocyte Disorders Team
WUMC has a critical mass of investigators in Hematology, Oncology, and Pediatric Hematology-Oncology
studying hematopoietic stem cell disorders such as Diamond-Blackfan anemia, Fanconi anemia, acquired
aplastic anemia, congenital neutropenia, myeloproliferative neoplasms (MPN), and myelodysplastic syndrome
(MDS), as well as inherited leukocyte disorders such as chronic granulomatous disease. Investigations of
these disorders have led to advances in understanding DNA repair, cell cycle control, hematopoiesis, and
leukemogenesis. They also are useful models for developing cellular therapy.
Hemostatic and Thrombotic Disorders Team
WUMC has been a center of world-class hemostasis research for more than four decades. Contributions
include the discovery and characterization of several hemostatic proteins, and the cloning of genes for
numerous hemostatic factors in blood, platelets and endothelial cells. These advances led to a fundamental
reorganization of our understanding of blood clotting and its regulation, to the molecular mechanism by which
aspirin inhibits platelet function, to major advances in understanding cell signaling pathways, to new clinical
diagnostic tests, and to clinical trials in the prevention and treatment of thrombosis. These accomplishments
provide a strong foundation for Scholars to conduct research on hemostatic and thrombotic disorders.
Hemoglobinopathies and Transfusion Medicine Team
WUMC provides care for the majority of children and adults with sickle cell disease in the St. Louis metropolitan area, and has become a national resource for innovative multidisciplinary clinical research in sickle cell disease. Our transfusion medicine services support one of the largest bone marrow transplantation services in the country. These accomplishments provide a strong foundation for the proposed Career Development Program.
John P. Atkinson, M.D.
Samuel B. Grant Professor of Medicine
Professor, Molecular Microbiology
John P. Atkinson, M.D., is Samuel B. Grant Professor of Medicine, Professor of Molecular Microbiology,
and Interim Chief of the Division of Rheumatology. Throughout his career, Dr. Atkinson has focused on basic,
translational and clinical studies of the complement system. He discovered a multigene family of receptor and
regulatory proteins that inhibit complement activation and serve as receptors for complement-opsonized
antigens, and has pioneered the characterization of mutations in complement proteins that predispose to
atypical HUS. Dr. Atkinson has participated in the development of complement protein derivatives that are in
clinical trials as inhibitors of complement activation. This past year, Dr. Atkinson and colleagues identified
mutations in the complement system's alternative pathway that are associated with preeclampsia in targeted
Morey A. Blinder, M.D.
Professor of Medicine
Professor of Pathology and Immunology
Dr. Blinder is an outstanding clinician with particular expertise in disorders of red cells, platelets, and blood coagulation. He was WUMC Outstanding Teacher of the Department of Internal Medicine (1994-5), received the Neville Grant Award for Clinical Excellence (1999), and was appointed to the Missouri Genetic Disease Advisory Committee by Gov. Holden (2004). He has published clinical studies or case reports of patients with bone marrow failure, sickle cell disease, heparin-induced thrombocytopenia, thrombotic thrombocytopenic purpura, and autoimmune acquired bleeding disorders. Several of these papers represent mentored clinical research by fellows in Hematology-Oncology or Laboratory Medicine. Dr. Blinder's clinics and inpatient service are outstanding resources for teaching the clinical management of non-malignant hematologic diseases as part of the Clinical Core Curriculum, and for patient-oriented Mentored Research Experiences. Dr. Blinder's interest in and knowledge of hemostatic disorders is reflected in the large numbers of patients with these disorders that he follows and also sees as new patients or in consultation. Dr. Blinder also has the largest clinic population in the region of adult patients with sickle cell disease. Therefore, he is well suited to participate as a Mentor as part of both the Hemostatic and Thrombotic Disorders Team and the Sickle Cell Disease and Other Hemoglobinopathies Team.
George J. Broze, Jr., M.D.
Professor of Medicine and Cell Biology & Physiology
Dr. Broze is a recognized expert in disorders of hemostasis and thrombosis. His work has focused on the initiation and regulation of coagulation. Specific accomplishments include the initial isolation and characterization of human factor VII, human tissue factor (TF), tissue factor pathway inhibitor (TFPI), human protein Z and protein Z-dependent protease inhibitor (ZPI) and the generation of mouse models of tissue factor, TFPI, factor XI, thrombin-activatable fibrinolysis inhibitor (TAFI), protein Z, and ZPI deficiency. His research has led to a now widely accepted revised coagulation cascade in which factor VIIa/TF complex regulated by TFPI is responsible for the initiation of coagulation that is amplified through the actions of factors VIII and XI. In this cascade, factor XI, activated by thrombin, serves a supplementary role by generating additional factor IXa and factor XII and other "contact factors" of the previous intrinsic pathway are not required for hemostasis. Decreased thrombin production due to deficiencies of factors VIII or IX (hemophilia A or B) leads to reduced TAFI activation, fibrin clot instability, and delayed bleeding. The role of the previously unrecognized PZ/ZPI anticoagulant pathway, which regulates factor Xa, factor IXa, and factor XIa activity, is currently being defined. Project areas for which he could be a Mentor include: clinical comparisons of anticoagulant strategies (e.g., heparin versus fondiparinux for prophylaxis of venous thromboembolism; warfarin versus warfarin plus vitamin K for secondary prevention of venous thromboembolism), disorders of hemostasis in diabetes (e.g., vascular levels of TFPI( and TFPI( in type 2 diabetic patients), and the role of PZ/PZI in fetal wastage and obstetrical complications.
Kenneth R. Carson, M.D.
Assistant Professor of Medicine
Dr. Carson is a hematologist and medical oncologist who specializes in the treatment of patients with lymphoproliferative diseases. He is also a health services researcher primarily interested in issues related to cost, quality, and access to care. In his current research projects, he is using large patient databases to perform observational studies in order to better understand the influence of age, race, and co-morbidities such as obesity on clinical treatment patterns and outcomes in patients with hematologic malignancies. Given his dual training in hematology and medical oncology, one outcome of particular interest is the incidence of thromboembolic events in patients with cancer. Through identification of risk factors associated with thromboembolism, he hopes that patients can be risk stratified to identify sub-populations in whom a primary prophylactic strategy with anticoagulation therapy may be appropriate.
Mary C. Dinauer M.D., Ph.D.
Fred M. Saigh Distinguished Chair of Pediatric Research
Professor of Pediatrics and of Pathology and Immunology
Scientific Director, Children's Discovery Institute
Dr. Dinauer studies the leukocyte NADPH oxidase and the role of oxidant production by neutrohils and macrophages in microbial killing, the inflammatory response and regulation of adaptive immunity. Other studies focus on the development of gene replacement therapy for X-linked CGD, utilizing viral vectors to introduce the corrective gene into murine and human hematopoietic stem cells, and novel conditioning strategies for marrow transplantation. These questions are being studied using a combination of molecular and cell biology approaches and animal models, including mice generated by gene targeting.
John F. DiPersio, M.D., Ph.D.
The Virginia E. and Sam J. Golman Professor of Medicine
Professor of Pediatrics and Pathology
Dr. DiPersio also is Chief, Division of Oncology; Director, Section of Bone Marrow Transplantation & Leukemia; and Deputy Director, Siteman Cancer Center. His research interests include the control of GVHD using gene therapy, the genetic and epigenetic events associated with relapsing acute myelogenous leukemia, the biology of stem cell mobilization, and the treatment of myelodysplastic syndrome. He is responsible for the development and oversight of the superb clinical research infrastructure of the Siteman Cancer Center, which will support a substantial amount of the clinical research conducted under this Program. Dr. DiPersio has mentored many academic physician-scientists who are conducting patient-oriented clinical research in bone marrow transplantation. Dr. DiPersio has great expertise in MDS, stem cell transplantation and the conduct of translational and clinical research, and will be an excellent Mentor for Scholars investigating the use of stem cell transplantation for bone marrow failure syndromes, MDS, or hemoglobinopathies.
Charles S. Eby, M.D.
Professor of Pathology and Immunology
Associate Chief, Division of Laboratory and Genomic Medicine
Professor of Internal Medicine
Dr. Eby conducts translational research in the development and application of clinical laboratory testing for non-malignant hematologic diseases. As co-investigator with Brian Gage, Dr. Eby designed and completed both retrospective cohort and prospective pilot studies that combine clinical, demographic, and pharmacogenetic information to explain 50% of the variation in therapeutic warfarin dosing. Dr. Eby also directed the central laboratory for the PREVENT study of secondary prevention of VTE, conducting coagulation testing and genotyping for factor V Leiden and Prothrombin gene 20210 SNP. The laboratory maintains a plasma and DNA archive of these study subjects for future investigations. Dr. Eby will be an excellent Mentor for projects related to his major research interests such as: rapid pharmacogenomic testing for initiation of warfarin therapy; molecular and functional immunologic characterization of cardiothoracic surgery patients at risk for heparin-induced thrombocytopenia; near-patient hemostasis testing during liver transplantation; standard and novel biomarkers for diagnosis and monitoring treatment of anemia of chronic inflammation; and genetic risk factors for post-phlebitic syndrome.
Brian F. Gage, M.D., M.Sc.
Professor of Medicine
Medical Director, Barnes-Jewish Hospital Blood Thinner Clinic
Medical Director, Barnes-Jewish Hospital and Washington University Physicians Network Anticoagulation Service
Dr. Gage also is the Director of the BJH Blood Thinner Clinic. He investigates the pharmacogenetics of antithrombotic therapy and thromboembolic events in patients with atrial fibrillation. He and his colleagues developed and are validating clinical prediction rules for stroke ("CHADS2") and for bleeding ("HEMORR2HAGES") among patients treated for atrial fibrillation. He is the PI for the National Registry of Atrial Fibrillation II dataset of 23,657 deidentified patient records from the National Stroke Project. His studies have quantified the costs, risks, and benefits of warfarin therapy and newer anticoagulants (e.g. direct thrombin inhibitors). His group recently identified a new side effect of warfarin: osteoporotic fractures. Dr. Gage also is using pharmacogenetics to improve the safety and effectiveness of warfarin therapy. A recent collaboration with geneticists discovered several polymorphisms that predict warfarin sensitivity and may permit the estimation of a safe warfarin dose a priori, rather than by trial-and-error. Dr. Gage maintains archived DNA from 1549 patients taking warfarin, and 200 cases/200 controls from a gastrointestinal hemorrhage study. He could be a Mentor for projects such as: characterization of hemostatic protein polymorphisms that affect warfarin therapy; role of VKORC1 in vitamin K-dependent pathology including arterial calcification; epidemiology of hemorrhage and thrombosis in atrial fibrillation.
Brenda J. Grossman, M.D., M.P.H.
Associate Professor of Pathology & Immunology
Medical Director, WUMC Blood Bank
Director, Transfusion Medicine Fellowship Training Program
Dr. Grossman is a member of the AABB Transfusion Practice committee and has served on the board of directors of the American
Association of Blood Banks (AABB) and as a member of the American National Red Cross Medical Advisory Committee. Under her direction, the blood bank performs high complexity reference work. Her research focuses on clinical aspects of transfusion medicine, especially for organ transplant recipients. She has extensive experience in cytopheresis and plasmapheresis and oversees red cell exchange transfusions at
WUMC, including prophylactic regimens for patients with sickle cell disease.
Monica L. Hulbert, M.D.
Assistant Professor of Pediatrics
Director, Pediatric Sickle Cell Disease Program
Monica Hulbert is an Assistant Professor of Pediatrics and the Director of the Sickle Cell Disease Program at St. Louis Children's Hospital. Dr. Hulbert possesses expertise in the pathophysiology of sickle cell disease, its associated comorbidities and clinical sickle cell disease care. She focuses her clinical research on the cerebrovascular complications of sickle cell disease, specifically cerebral vasculopathy and stroke. Approximately 400 patients are followed in the pediatric Sickle Cell Disease Program at St. Louis Children's Hospital.
Allison A. King, M.D., M.P.H.
Assistant Professor of Occupational Therapy and Pediatrics
Dr. King is a member of the Patient-Oriented Research Unit in Pediatrics, and is interested in educational outcomes and interventions related to brain injury. She is particulary interested in patients with sickle cell disease, with and without cerebral infarcts. Her studies have addressed the poor educational attainment in students with sickle cell disease, probed the possible barriers to educational outcomes for these students, intervened in the school setting with a rehabilitation program, and educated these students' teachers about the common issues such students face. She continues to expand on investigations and interventions for children with sickle cell disease and cognitive deficits. Dr. King will be an excellent mentor for clinical studies in sickle cell disease including: educational outcomes in children; psychosocial aspects in children; psychological function of parents.
Jin-Moo Lee, M.D., Ph.D
Professor of Neurology, Radiology, and Biomedical Engineering
Director, Cerebrovascular Disease Section
Department of Neurology
Director, Animal Surgery Core
The Hope Center for Neurological Disorders
Dr. Lee also is the Director of the Cerebrovascular Disease Section and Program Director of the Neurovascular Residency in the Department of Neurology. Dr. Lee's clinical expertise is in stroke neurology. He attends on the inpatient stroke service, and is an attending physician in the Comprehensive Outpatient Stroke Clinic. He has participated in numerous clinical trials for the treatment and neuroimaging of acute ischemic stroke patients. Dr. Lee is a recipient of the Zaritsky Research Award and the Arthur K. Asbury Resident Award for Clinical Excellence. In addition, he was awarded the Clinical Teacher of Year Award by the Washington University Medical Students, and the Sven Eliasson Award for Teaching Excellence by the Neurology Residents in 2000.
Timothy J. Ley, M.D.
Alan A. and Edith L. Wolff Professor of Medicine
Professor of Genetics
Director of the Stem Cell Biology Section of the Oncology Division
Associate Director for Cancer Genomics of the Genome Sequencing Center
Dr. Ley investigates cytotoxic lymphocytes use granzymes to kill target cells, the regulation of myeloid gene expression in acute leukemia, mouse models of sickle cell anemia, and the use of homologous recombination for gene therapy of single gene disorders. His laboratory identified several cis-acting regulatory elements involved in globin gene regulation and switching, including the mouse locus control region. At the NIH, he helped to perform clinical trials using 5-azacytidine to augment fetal hemoglobin synthesis in patients with beta-thalassemia and sickle cell anemia. These trials ultimately led to the use of hydroxyurea as standard therapy in patients with severe sickle cell anemia. His laboratory has made a beta-6 isoleucine substitution in the beta-major globin gene of mice, creating a new beta globin gene mutation in mice for use in gene correction studies. For example, he is investigating methods to improve the efficiency of homologous recombination in primary hematopoietic cells for gene therapy of hemoglobinopathies, including sickle cell disease. Dr. Ley would be an excellent Mentor for related research projects including: transfection studies of human hematopoietic progenitor cells from patients with hemoglobinopathies; homologous recombination in primary hematopoietic progenitor cells, using sickle cell disease as the model; the phenotype of the beta-6I mutation in mouse models of sickle cell anemia.
Daniel C. Link, M.D.
Professor of Medicine and Pathology
Dr. Link is a leader in the study of hematopoietic growth factors (particularly G-CSF), congenital neutropenia, and stem cell mobilization. His studies led to the demonstration that G-CSF is the principal growth factor regulating neutrophil homeostasis, that neutrophil release from the marrow is regulated primarily by stromal derived factor-1 (SDF-1), and that G-CSF induces HSC mobilization by potently inhibiting osteoblast function, which decreases SDF-1 expression and ultimately induces HSC mobilization. Dr. Link has advanced our understanding of severe congenital neutropenia and of how G-CSF receptor mutations promote the progression to acute leukemia in this patient population. His major research interests include: 1) The pathogenesis of congenital neutropenia including severe congenital neutropenia, WHIM syndrome, and Shwachman Diamond syndrome. 2) Mechanisms of hematopoietic stem cell mobilization. 3) Mechanisms of endothelial progenitor cell induced angiogenesis. 4) Translational potential of endothelial progenitor cell mobilization to mediate therapeutic angiogenesis. He could be a Mentor for projects in these areas such as: genetic testing in congenital neutropenia to identify patients at risk for leukemic progression, and novel causative mutations; clinical trials of G-CSF or AMD3100 to induce endothelial progenitor mobilization for therapeutic angiogenesis in peripheral vascular disease; clinical trials of endothelial progenitor infusions after angioplasty to stimulate re-endothelialization and prevent restenosis.
Elaine M. Majerus, M.D., Ph.D.
Associate Professor of Medicine
Division of Hematology
Dr. Majerus investigates ADAMTS13, a metalloprotease involved in the pathogenesis of thrombotic microangiopathy. Dr. Majerus was involved in cloning ADAMTS13 and has published several peer-reviewed articles on the structure and function of this enzyme. Her research interests include: 1) interaction of ADAMTS13 with endothelial cells and platelets; 2) cofactors affecting ADAMTS13 activity; and 3) the role of the vascular endothelium and plasma proteins in other thrombotic microangiopathies. Dr. Majerus joined the faculty in July, 2005, and will be an outstanding Mentor for projects related to the molecular pathogenesis of thrombotic microangiopathy, such as: the effect of heparin treatment on ADAMTS13 activity in vivo; complement inhibitors as therapy for thrombotic microangiopathy; inflammatory biomarkers for thrombotic microangiopathy.
Diane F. Merritt, M.D.
Professor of Obstetrics and Gynecology
Dr. Merritt also is the Director of the Division of Pediatric and Adolescent Gynecology. Dr. Merritt is a founding member of the North American Society of Pediatric and Adolescent Gynecology. She is a member of the American College of Obstetricians and Gynecologists (ACOG) Committee on Adolescent Health Care, and the Advisory Committee for Reproductive Health Drugs for the Food and Drug Administration. Over the last 20 years, Dr. Merritt has pioneered the Program in Pediatric and Adolescent Gynecology at WUMC, which is now an established major referral center in the Midwest, and a site for training students, residents and fellows in Pediatric and Adolescent Gynecology. Dr. Merritt is a nationally and internationally recognized expert in pediatric and adolescent gynecology and women's health, and the recipient of many teaching and clinical awards. Dr. Merritt is known for her clinical work in the diagnosis and treatment of genital injuries, as well as the diagnosis and repair of congenital anomalies of the reproductive tract, and the management of bleeding and hormonal disorders of puberty, perimenopause and menopause. She will be an excellent Mentor for clinical projects on topics such as: vaginal bleeding in pediatric patients; abnormal menstrual bleeding in adolescence; unique vaginal bleeding problems for patients undergoing solid organ or marrow transplantation; contraceptive options and menstrual management for adolescents with bleeding disorders or thrombophilia (e.g., factor V Leiden, protein C or S deficiency, ITP, sickle cell disease, systemic lupus erythematosis, von Willebrand disease). Although Dr. Merritt is listed for convenience under the Hemostatic and Thrombotic Disorders Team, her expertise and clinical resources will be valuable to any project that is related to women's health.
Robi D. Mitra, Ph.D.
Alvin Goldfarb Distinguished Professor of Computational Biology
Assistant Professor Genetics
Director of New Genomic Technologies, Genomics and Pathology Services
There is still a great deal to learn about the design principles that guide vertebrate development. Since all cells in an organism contain the same genes, transcribing different sets of genes is what confers a cell's specialized role. Which genes get turned on or off to create a particular cell type at the right time, in the right place during the development of an organism? This is one of the pivotal questions in developmental biology. We have developed a technology, Transposon "Calling Cards," to attack this question in a novel way, and we have shown that it works in yeast and mammalian cell culture and completed proof-of-principle experiments in living zebrafish. This technology can record gene expression along different cell lineages throughout the development of a living vertebrate. We will produce a complete record of gene activation at different stages of development, watching as cells and their progeny specialize and form organs. These data will contribute to the field by providing a blueprint for the generation of many cell types, and could ultimately guide the reprogramming of embryonic or induced pluripotent stem cells to produce specific cell types.
J. Evan Sadler, M.D., Ph.D.
Professor of Medicine
Professor of Biochemistry and Molecular Biophysics
Chief, Division of Hematology
Dr. Sadler's background and research are described above under Program Leadership. His clinical research focuses on von Willebrand disease and thrombotic thrombocytopenic purpura and includes: 1) the role of VWF level as a risk factor for bleeding and thrombosis; 2) pathogenesis, diagnosis, classification and treatment of VWD; 3) development of rapid ADAMTS13 assays for clinical use in thrombotic microangiopathy; 4) novel mechanism-based treatments for thrombotic microangiopathy. Both von Willebrand disease and thrombotic thrombocytopenic purpura commonly affect women of childbearing age. He could be a Mentor for clinical research projects investigating: the relationship of VWF level to the risk of peripartum hemorrhage; prevalence of low VWF in women with menorrhagia; evaluation of DDAVP for prophylaxis and treatment of bleeding in VWD; outcomes of plasma exchange therapy in idiopathic thrombotic thrombocytopenic purpura and non-idiopathic thrombotic microangiopathy; outcome of platelet transfusions in thrombotic microangiopathy; development and clinical evaluation of rapid assays for ADAMTS13 in thrombotic microangiopathy; ADAMTS13 inhibitor titer as a risk factor for refractory or relapsing TTP; efficacy of rituximab as adjunctive initial therapy for high-risk TTP; development and validation of a registry and database for patients with thrombotic microangiopathy.
Mark S. Sands, Ph.D.
Professor of Medicine and Genetics
Dr. Sands is developing new gene therapy methods to treat a variety of inherited diseases. He is focusing on a group of lysosomal storage diseases caused by deficiency in one of the acid hydrolases that are normally located in lysosomes. The absence of these lysosomal enzymes typically causes widespread accumulation of intermediate degradation products in most tissues, leading to organomegally, skeletal dysplasia, retinal degeneration, cardiac insufficiency, and cognitive defects. Dr. Sands has shown that bone marrow transplantation or direct enzyme replacement can prevent most signs of disease in a mouse model of mucopolysaccharidosis VII, which is caused by defects in beta-glucuronidase. More recently, he has shown that gene therapy with beta-glucuronidase constructs in adeno-associated virus (AAV) vectors can improve retinal function and reduce CNS damage. His encouraging results with a human immunodeficiency virus (HIV)-based vector in hematopoietic stem cells from a human MPS VII patient are the basis for a proposed clinical trial of gene therapy for this disease. Dr. Sands would be an excellent Mentor for preclinical or translational research projects on gene therapy.
Shalini Shenoy, M.D.
Professor of Pediatrics
Director, Pediatric Stem Cell Transplant Program, St. Louis Children's Hospital
Dr. Shenoy is a member of the Patient-Oriented Research Unit in Pediatrics, and she investigates reduced intensity conditioning and allogeneic stem cell transplantation for non-malignant disorders. She has pioneered a novel conditioning strategy using immunosuppression instead of myeloablation that has allowed successful transplantation in several patients with non-malignant hematologic disorders. The success of her pilot trials has resulted in the approval of a national trial for unrelated donor transplantation in high-risk sickle cell disease. This important, high-profile trial is will be supported by the cIBMTR and the BMT CTN, and will provide many opportunities for outstanding clinical research projects. Dr. Shenoy also investigates the treatment of hematologic cytopenias with targeted anti-lymphocyte agents. In preliminary studies, approximately 25% of patients were found to have a Fas-mediated death defect in lymphocytes, similar to that recognized in patients with the autoimmune lymphoproliferative syndrome. Good responses to rituximab were obtained in several refractory patients. Dr. Shenoy's knowledge of immunology, and her groundbreaking studies of stem cell transplantation in non-malignant blood diseases, set the stage for exciting and productive mentored research projects for our Scholars such as: reduced intensity conditioning and allogeneic stem cell transplantation for bone marrow failure syndromes, immune dysregulation, metabolic disorders, and hemoglobinopathies; and rituximab treatment in autoimmune hemolytic anemia, neutropenia, or thrombocytopenia.
Philip C. Spinella, M.D.FCCM
Associate Professor of Pediatrics
Director, Critical Care Translational Research Program
Dr. Spinella was an active duty US Army physician for 12
years, including a year in Iraq. He is a consultant to the US Army Blood Research Program and the American
Association of Surgery for Trauma Curriculum Committee, and chairs the Transfusion, Immunology and
Coagulation in Kids (TRICKS) research network in the US and Canada. His research includes blood
component and whole blood resuscitation for traumatic hemorrhagic shock; the effects of RBC storage
duration on outcomes, immunology and coagulation; and coagulation monitoring by thromboelastography. He
has demonstrated an association between increased plasma, platelet and whole blood administration and
improved survival for combat casualties. His current projects examine the immunologic, coagulation, and
vasoregulatory effects of red cell transfusion according to storage age in two large randomized trials (ABLE
and RECESS). He is also the Co-PI of a proposed randomized trial to determine if RBC storage age increases
the risk of multiple organ dysfunction syndrome (MODS) in critically ill children.
Douglas M. Tollefsen, M.D., Ph.D.
Professor of Medicine
Dr. Tollefsen is interested in proteins that regulate the activity of thrombin. One of these is heparin cofactor II (HCII), a plasma protein that inhibits thrombin by formation of a covalent 1:1 complex. Dermatan sulfate and heparan sulfate bind to HCII and increase the rate of thrombin inhibition >1000-fold. Biosynthesis of these glycosaminoglycans by cells in the vessel wall may determine the site of action of HCII in vivo. The Tollefsen laboratory has characterized the specific oligosaccharide sequences in dermatan sulfate that stimulate HCII, and has engineered knockout mice with HCII deficiency that exhibit increased susceptibility to arterial thrombosis. His research interests include: 1) the cause of neonatal mortality in HCII-deficient 129/SvJ mice and interactions of HCII deficiency with other thrombophilic mutations; 2) activation of HCII in vivo upon binding to dermatan sulfate in the vessel wall or in other tissues; 3) the role of HCII in determining the location and amount of thrombin activity and the time course of smooth muscle cell and macrophage accumulation in neointimal and atherosclerotic lesions; 4) comparative analysis of HCII-binding dermatan sulfate oligosaccharides from porcine skin, mucosa, vascular smooth muscle, and fibroblasts. Dr. Tollefsen would be an excellent Mentor for clinical research projects related to his interests in hemostasis and anticoagulation, such as: laboratory investigaton of patients with rare bleeding or thrombotic disorders; assessment of physician and patient compliance with best practice standards for anticoagulant use; the causes and outcomes of cytopenias in ICU patients.
Matthew J. Walter, M.D.
Associate Professor of Medicine and Genetics
Dr. Walter's major research interests include: (1) the discovery of mutations within the genomes of hematopoietic cells from patients with MDS by utilizing high-resolution oligomer-based array comparative genomic hybridization and mutational profiling; (2) addressing whether a heterozygous mutation in a gene(s) located on human 5q31.2 is associated with MDS; (3) abnormal erythroid development in the setting of haploinsufficiency for specific gene(s) on human chromosome 5q31.2. He is a recipient of a highly competitive Scholar Award from the American Society of Hematology, and is supported by grants from the Aplastic Anemia & MDS International Foundation, the Center for Genome Sciences, and the NIH/NHLBI. Dr. Walter will be an excellent Mentor for clinical research projects on bone marrow failure syndromes including MDS, such as: prevalence of specific candidate gene mutations in bone marrow failure syndromes; gene expression profiling for classification and prognosis in bone marrow failure syndromes; array comparative genomic hybridization to define clonal chromosomal abnormalities in bone marrow failure syndromes; development and validation of a registry and database for patients with bone marrow failure syndromes.
David B. Wilson, M.D., Ph.D.
Associate Professor of Pediatric Hematology-Oncology and Developmental Biology
Dr. Wilson investigates the biological function of GATA-binding proteins, a group of zinc finger transcription factors implicated in mesoderm and endoderm development (including hematopoiesis). His clinical interests include bone marrow failure syndromes, congenital dyserythropoietic anemias, and congenital and acquired platelet disorders. With Monica Bessler and Philip Mason, Dr. Wilson investigates the pathogenesis of bone marrow failure, with a focus on genes involved in telomerase function such as TERC and TERT. He could be a Mentor for related research projects such as: development and validation of a registry and database for pediatric patients with bone marrow failure; penetrance and expressivity of TERC mutations in patient with bone marrow failure; prevalence and clinical significance of mutations in RPS19, a gene implicated in Diamond-Blackfan anemia, in patients with "idiopathic" aplastic anemia; impact of TERT deletions on the clinical phenotype of patients with 5p- (Cri du chat) syndrome; prevalence and clinical significance of GATA transcription factor mutations among patients with congenital dyserythropoietic anemia and "idiopathic" thrombocytopenia; clinical significance of ELA2 mutations and an exaggerated "misfolded protein response" in pediatric patients with severe congenital neutropenia (in collaboration with Dr. Daniel Link); prevalence and pathogenesis of hypertriglyceridemia among infants with severe hemolytic anemia (e.g., pyruvate kinase deficiency).