Hematologic Malignancies, Blood and Marrow Transplant (BMT) and Cellular Therapy
The BMT & Cellular Therapy Program at the Medical College of Wisconsin is one of the oldest and among the largest programs in Midwest performing over 350 procedures annually. The program is internationally recognized for world class patient care, excellent survival outcomes and cutting-edge research. Each year over 35% of transplant and cellular therapy procedures by the program are done of interventional clinical trials, placing the program among the best in country in terms of trial activity ratio. As one of key core centers for the BMT CTN trials networks, MCW faculty are behind the inception, design and execution of practice changing trials looking at the role of optimal GVHD prevention following allogeneic transplantation, treatment of high risk and refractory GVHD, optimal donor selection, pre transplant frailty assessment, and application of early CAR-T application in high risk myeloma, to name a few. The program is leading the nation in terms of application of gene therapies in non-malignant blood disorders and known expertise in utilizing allogeneic transplantation as a curative therapy in Sickle Cell Disease. The program is also a key site for industry sponsored trials looking at novel Cellular Therapy platforms including TCR-based therapies and Tumor Infiltrating Lymphocytes for solid tumors, third-party CAR-T and NK cell-based platforms of lymphomas and myeloma, and TCR-like treatments for acute and chronic leukemia. The robust portfolio of investigator lead research at the program involves novel conditioning approaches for alternative donor transplantation, steroid free GVHD treatments, antibody based GVHD prevention strategies, and post-transplant immune modulation to eradicated measurable residual disease.
Dr. Atallah's primary interest is in the treatment of patients with leukemia, myelodysplastic syndromes (MDS) and myeloproliferative disorders with special emphases on the treatment of patients with chronic myelogenous leukemia (CML). He is co-Principal Investigator (PI) with Dr. Kathryn Flynn, MD on an R01 from the National Cancer Institute (NCI) to evaluate stopping tyrosine kinase inhibitors in patients with CML who are in complete molecular remission. He is currently the administrative director of the Jean Khoury Cure CML consortium (HJKC3) which is housed at MCW. In addition, he is the Clinical basket chair for patients < 60 with AML in the NCI myelomatch precision medicine initiative.
Dr. Carlson's research focus is on hematopoiesis. Using a novel mouse model system, she has identified a requisite component of the early lymphopoietic niche. She is now working to elucidate the biochemical regulation of this niche and its spatial localization within the bone marrow. Her research activities provide information about the basic biology of the hematopoietic stem cell and early lymphocyte developmental environment and characterize new targets for niche-directed therapy. Her long-term goal is to identify novel targets for the treatment of bone marrow failure syndromes and hematopoietic malignancies. Dr. Carlson is the recipient of a K08 mentored career development award from the National Heart Lung and Blood Institute.
Dr. Chen's research focuses on the role of micronutrients in regulating graft-versus-host disease (GVHD). His lab is investigating how vitamin A and vitamin D affect GVHD risk after allogeneic stem cell transplantation using animal models. He is also investigating how to target nuclear receptors to mitigate GVHD. Ongoing research uses genetic, nutritional, and pharmacological approaches to examine the complex interactions among the intestinal mucosal barrier, gut microbiota, and donor immune cells in the setting of experimental GVHD.
Dr. Chhabra is a BMT-trained clinician with interest in BMT and multiple myeloma. His current research interests include clinical trials for drug development in the areas of plasma cell neoplasms and improving outcomes of allogeneic hematopoietic cell transplantation. He is the Principal Investigator (PI) for an Investigator-Initiated study evaluating the utility of anti-IL-6 monoclonal antibody tocilizumab for prevention of Graft-versus-Host Disease (GVHD) in patients receiving allogeneic transplant for hematologic malignancy. He is also the site PI for a number of phase I and II clinical trials for treatment of newly diagnosed and relapsed/refractory multiple myeloma and for treatment of GVHD. He is also actively involved with transplant registry studies, as Scientific Director of Regimen-Related Toxicity Working Committee of the Center for International Blood and Marrow Transplant Research (CIBMTR).
Dr. Cusatis is an Assistant Professor of Medicine at the Medical College of Wisconsin, Division of Hematology and Oncology. She is a faculty member of the Center for International Blood and Marrow Transplant Research (CIBMTR). Her research focuses on the intersection of patient reported outcomes, social determinants of health, and time use patterns to understand patient and caregiver health outcomes. Through mixed methods approaches, she collaboratively works on projects analyzing patient reported outcomes, patient/provider communication, decision making, and financial toxicity among transplant and cellular therapy patients and other contexts.
Dr. D’Souza is an Associate Professor of Medicine with a research focus in plasma cell disorders including multiple myeloma and amyloidosis. She is the Scientific Director of the Plasma Cell Disorders and Adult Solid Tumors working committee of the CIBMTR. In addition to conducting clinical trials, she also leads efforts to study quality of life and patient-reported outcomes in these diseases. She mentors multiple trainees on research projects in this area.
Dr. Dhakal's research focuses on multiple myeloma and related plasma cell disorders. He completed two early phase studies in multiple myeloma: one looking at the novel drug combination in the management of relapsed/refractory multiple myeloma and the other on the pharmacokinetics of new Melphalan both of which were published. He has secured funding for two more early phase studies: one looking at the novel induction therapy in multiple myeloma patients with renal injury, and that also evaluates the role of novel biomarker for renal recovery. The other study is an entirely new drug targeting PIM kinase with the study evaluating a dual role of anti-myeloma and bone protective effect. He was awarded a pilot grant from American Cancer Society to explore the role of micro-RNA in multiple myeloma bone disease and the results looking promising to be tested in a larger setting. Additionally, in collaboration with investigator from University of Wisconsin Madison/UCSD, he was awarded a prestigious Translational Research Program grant from Leukemia and Lymphoma Society to explore the role of matrikines in the immune regulation of myeloma. This concept is being investigated prospectively through a nationally conducted multi-center BMT CTN study.
Dr. Dong's research focuses on integrating high throughput “omics” data into epidemiological studies to develop approaches to reduce cancer burden and cancer disparities. She has applied genome-wide association study (GWAS), next generation sequencing (NGS), gene-environment interaction and Mendelian Randomization analysis approaches to identify genetic and non-genetic risk factors of cancer. After she joined MCW, she expands her interests to understand genetic determinants underlying outcomes of patients undergoing hematopoietic cell transplantation.
Dr. Drobyski's laboratory evaluates multiple aspects of the immunobiology of allogeneic HCT with particular emphasis on Graft-versus-Host Disease (GVHD) biology. By employing murine models of stem cell transplantation, this research aims to understand the interplay between the inflammatory and regulatory arms of the immune system and how they impact the severity of GVHD. He is also the Leader of the Discovery and Development Therapeutics Program of the MCW Cancer Center. Dr. Drobyski has been continuously funded by NIH for this work since 1991. He currently has three NIH grants that are directed at understanding the pathophysiology of GVHD and is particularly interested in developing new approaches for the prevention of this disease in the gastrointestinal tract which is the major site of morbidity in patients. He also has an interest in the translation of pre-clinical studies into the clinic to attenuate GVHD and currently has two ongoing clinical trials designed to prevent GVHD in allogeneic hematopoietic stem cell transplant recipients.
Dr. Eapen's research focus is on use of alternative donor and grafts for allogeneic hematopoietic cell transplant for acute leukemia and non-malignant hematologic diseases like aplastic anemia and sickle cell disease. Her work has identified optimal strategies in selection of unrelated adult donors and umbilical cord blood units for transplantation. She has led comparative effectiveness studies that have addressed using mismatched related donors (haploidentical relatives) and unrelated donors for hematologic malignant and non-malignant diseases. She has collaborated with external investigators in developing the first NIH funded phase II clinical trial of gene therapy for sickle cell disease. She is also the current Chair, Data Consortium, for the National Heart Lung and Blood Institute’s Cure Sickle Cell Initiative.
Dr. Fenske's clinical and research interests focus on the care of patients with lymphoma. He has a strong interest in refining the use of hematopoietic cell transplantation (HCT) as a treatment for lymphoma. He is a co-chair of the Lymphoma Working Committee of the Center for International Blood and Marrow Transplant Research (CIBMTR). He is the co-chair of a national (Intergroup) trial evaluating the use of maintenance therapy with ibrutinib to prevent recurrence of diffuse large B-cell lymphoma after autologous HCT. He is also the national Principal Investigator for an Intergroup trial evaluating a deep sequencing minimal residual disease assay to help direct therapy for mantle cell lymphoma patients in first remission.
Dr. Flynn is the Senior Scientific Director for Patient-Reported Outcomes in the Center for International Blood and Marrow Transplant Research (CIBMTR). Her research focuses on the measure development and analysis of patient-reported outcomes as well as mixed methods approaches to understanding and improving patient-provider communication and patient decision making. She leads the NIDDK-funded Wisconsin Exploratory Center for Interdisciplinary Research in Benign Urology.
Dr. Guru Murthy's clinical and research interests focus on the outcomes of patients with leukemia and stem cell transplantation. He conducts retrospective and prospective clinical studies in patients with leukemia and stem cell transplantation with a goal of improving disease related outcomes.”
Dr. Hamadani's research interest includes lymphoma, GVHD, and alternative donor transplantation. He is the Scientific Director of the CIBMTR’s Lymphoma Working Committee, and the Medical Director of MCW BMT and Cell Therapy Program. He has investigated the role of immunomodulation with HMG-CoA reductase inhibitors and TNF-alpha blockers for preventing acute GVHD as well as the role of the novel proteasome inhibitor MLN9708 in preventing chronic GVHD. As part of BMT CTN’s Data Coordinating Center, Dr. Hamadani is intricately involved in the development and conduct of several cooperative group trials looking at prevention and treatment of GVHD, and mitigation of post-transplant relapse-risk in acute leukemias.
Dr. Hari conducts clinical research evaluating novel therapies for plasma cell disorders including myeloma and amyloidosis as well as novel approaches for transplantation. He is the Scientific Director of the CIBMTR’s Plasma Cell Disorder Working Committee and co-Chair of multiple national trials for multiple myeloma. He is also an investigator on several novel drug phase I and II trials in multiple myeloma, several of which have led to FDA approval. In addition, he has projects in development for translational applications of cell-based therapeutics in malignancies, spinal cord injury, hemophilia and other immune therapies.
Dr. Horowitz is Deputy Cancer Center Director. Her career has focused on assessing clinical outcomes of blood and marrow transplantation (BMT) and other cell therapies through the Center for International Blood and Marrow Transplant Research (CIBMTR). She leads the BMT Clinical Trials Network (CTN), funded by NHLBI and NCI. The BMT CTN conducts large multicenter trials and enrolls patients from more than 100 centers in the US, Canada, France and Germany. Dr. Horowitz is co-PI, with Dr. Mary Eapen, of a grant from NHLBI for theCIBMTR to participate in NHLBI’s Cure Sickle Cell (CureSC) Initiative. The CIBMTR works with the CureSC Data Consortium to build a research data ecosystem designed to support investigator-initiated collaborative research. The CIBMTR also supports the design and launch of gene therapy sickle cell disease clinical trials using the infrastructure of the BMT CTN.
Dr. Janz's primary research interest concerns neoplasms of terminally differentiated, immunoglobulin producing B-lymphocytes called plasma cells. Relying in part on gene-insertion mice that mimic different fine structures of the human MYC-activating t (8;14) (q24;q32) translocation, he recapitulates important features of human plasma cell myeloma (multiple myeloma) in single and compound transgenic mice. His laboratory takes advantage of mouse models of this sort to elucidate mechanisms of neoplastic plasma cell development and evaluate new approaches to myeloma treatment and prevention. The long-term goal of Dr. Janz’ work, which is supported by NCI R01CA151354, is to improve the outcome of patients with myeloma and related blood cancers. To that end, he collaborates with fellow investigators from HemOnc, MCW Cancer Center and Versiti Blood Research Institute.
Dr. Johnson conducts basic/translational research on adoptive T cell immunotherapies for both hematologic malignancies and solid tumors. He is also Director of the BMT Cell Therapy Laboratories, which processes hematopoietic progenitor cells and immune cells for the MCW Blood and Marrow Transplant Program and participates in the development of novel immune cell therapies for patients with cancers and other diseases. The labs also provide some immune monitoring services for investigators involved in immunotherapy clinical trials.
Dr. Kearl's research interest is in translational cancer immunotherapy. He is the Assistant Director of the BMT & Cell Therapy Laboratories and Co-Director of the new MCW Cancer Center shared resource – the Cell Therapy and Immune Monitoring Laboratory. The laboratory has developed expertise with in-house CAR-T cell manufacturing for early phase clinical trials. In addition, the laboratory provides cutting-edge immune profiling to support mechanistic and correlative studies of novel immunotherapies.
Dr. Malarkannan's research interests include signaling cascades that regulate the development and functions of human Natural Killer cells (NK) patients with malignancies, inherited diseases and infections, and developing translational models to improve the anti-tumor efficacy of human NK cells. His team uses cellular, biochemical, and transcriptomic (single-cell RNA-seq) approaches. Research in his laboratory is supported by NCI, NIH, MACC Fund, Nicholas Family Foundation, and Gardetto Family Endowed Chair.
Dr. Michaelis' research interests are in the care of patients with acute and chronic leukemias. She conducts research on novel agents in the treatment of these diseases and in ways to better manage the side effects and toxicities of therapies. She is the primary investigator of a national clinical trial being developed to test low-intensity therapy for older individuals who have acute myeloid leukemia.
Dr. Pasquini's research focus is on cellular therapies for the treatment of cancer. He oversees the CIBMTR cellular therapy registry and is the PI for the NCI-funded Cellular Immunotherapy Data Resource (CIDR). He also oversees clinical research on CT in the CIBMTR along with the conduct of long term follow up of commercial CAR T cells and other cellular therapies.
Dr. Runaas' research interests include improving outcomes for patients undergoing allogeneic bone marrow transplant by better understanding and preventing graft-versus-host disease and trying to optimize communication between patients with advanced hematologic malignancies and their providers. She hopes to continue to foster a translational and collaborative research career incorporating both qualitative and quantitative methods to improve the outcomes of patients with advanced hematologic malignancies.
Dr. Saber conducts clinical research evaluating outcomes of autologous and allogeneic HCT. He is the Scientific Director of the CIBMTR’s Chronic Leukemia, Acute Leukemia, and Health Services & International Issues Committees. His research primarily focuses on patients with MDS and on issues related to cost-effectiveness and access to HCT care. He is the protocol officer for a national clinical trial comparing transplantation to non-transplant therapies among older MDS patients (BMT CTN 1102). He is a co-principal investigator of an ancillary R01 grant to evaluate the cost-effectiveness of these two treatment approaches among older MDS patients participating in BMT CTN 1102.
Dr. Shah's research interests includes lymphoid malignancies, cellular and immunotherapy, and bone marrow transplant. He is leading the internal CAR-T cell trial for non-Hodgkin lymphoma at MCW and is working on developing new treatment regimens for patients with relapsed hematological malignancies.
Dr. Shaw has an interest in health-related quality of life and survivorship issues in patients who undergo hematopoietic cell transplantation (HCT). She is especially interested in the ability of patient reported outcome (PRO) collection to predict patient experience and clinical outcomes. She also has an interest in hematopoietic cell donors, both in terms of their experience and in terms of determining factors which help to select the best donor for an individual patient.
Dr. Zamora's research spans the fields of viral and cancer immunology, with a special focus on identifying ways to modulate the immune system to more effectively target and eliminate virally infected or cancerous cells. Along these lines, the lab utilizes cellular-based engineering approaches that aim to increase the specificity of immune cells for their targets and at the same time decrease the likelihood of off-target toxicities. A longstanding goal in the lab has also been to help address the current disparities in cancer research by developing reagents, assays, and tools that provide a deeper understanding of the underlying mechanisms that govern antitumor immunity across diverse demographic groups. Current research in the Zamora lab focuses on: (1) discovering tumor antigens that serve as immunogenic targets, (2) identifying the mechanisms involved in the immune system’s ability to generate antitumor specificities, (3) characterizing the phenotypic, functional, and receptor repertoires of NK cells and neoantigen-specific T cells, and (4) exploring ways to translate these findings in order to expand on the current therapeutic options used to treat cancer.