Hematologic Malignancies & Cellular Therapy (HMCT)

Program Overview
The Hematologic Malignancies and Cellular Therapy (HMCT) Research Program is a multidisciplinary basic, translational and clinical research effort whose overall goal is to improve outcomes for patients with hematologic malignancies. The broad, long-term goal of the HMCT program is to build on and extend the current knowledge in the fields of leukemia, lymphoma, myeloma, hematopoietic cell transplantation, and immunotherapy, and to develop and implement novel strategies for improving therapeutic results in these patients through a collaborative and integrated approach involving all the investigators in the program.
There are several areas of research. Broadly, these can be divided into: a) basic research into the tumor microenvironment, bone marrow niche, b) basic understanding of immunity, both inate and adaptive, c) genomics, including a genomics core, d) cellular therapies such as hematopoietic stem cells, adotive immunotherapy with selected T cells, NK cells, dendritic cell vaccines, gamma delta T cells, and e) graft-versus-host disease and graft-versus-leukemia effects, f) cell signaling pathways in normal and tumor cells. As a complement to these efforts, there is also a robust clinical trials office with over 100 active clinical trials specific to hematologic malignancies and transplantation. These range from phase I “first in humans” to randomized phase III studies.
Specific Aims
- To understand hematopoietic stem cell biology and optimize stem cell graft for allogeneic and autologous stem cell transplantation;
- To understand the basic biology of graft versus tumor (GvT) and graft versus host disease (GvHD), and to improve GvT without significant GvHD;
- To understand the biology of T, B and NK cells and develop novel immunotherapeutic strategies;
- To develop genomic signatures for hematologic malignancies and understand mechanisms underlying leukemogenesis or lymphomagenesis;
- To design and execute novel Phase I and Phase II clinical trials in hematologic malignancies based on novel laboratory discoveries within the program.
Focus Areas
- Hematopoiesis
- Immunity
- Leukemogenesis & Lymphomagenesis
- Clinical Trials
Leadership Bios
Nelson Chao, MD, is the Donald D. and Elizabeth G. Cooke Professor of Medicine and Immunology and chief of the Division of Hematologic Malignancies and Cellular Therapy at Duke University. He has been the leader of the Hematologic Malignancies and Cellular Therapy (HMCT) Research Program since he joined the Duke faculty in 1996. One of his major efforts is to foster interactions with laboratory based work and help with the transition to the clinical arena, bringing laboratory based protocols to the clinics and bringing clinical observations to foster laboratory research. Importantly, Chao has been instrumental in leading multi investigator grants, specifically the P-01 in hematopoietic stem cell transplantation and the Center for Medical Countermeasures Against Radiation (CMCR, U-19) which brings principal investigators from Duke as well as other academic institutions.
Stefanie Sarantopoulos, MD, PhD, is an established physician-scientist in the field of hematopoietic stem cell transplantation and human B cell signaling. Her work focuses on chronic graft versus host disease and the development of agents that improve safety and efficacy of cellular immunotherapy for hematolymphoid cancers.
Scientific Highlights
Brennan, TV, Lin, L, Brandstadter, JD, Rendell, VR, Dredge, K, Huang, X, and Yang, Y. "Heparan sulfate mimetic PG545-mediated antilymphoma effects require TLR9-dependent NK cell activation." The Journal of Clinical Investigation 126, no. 1 (January 2016): 207-219.
Quarmyne, M, Doan, PL, Himburg, HA, Yan, X, Nakamura, M, Zhao, L, Chao, NJ, and Chute, JP. "Protein tyrosine phosphatase-σ regulates hematopoietic stem cell-repopulating capacity." The Journal of Clinical Investigation 125, no. 1 (January 2015): 177-182.
Gao, F, Bonsignori, M, Liao, HX, Kumar, A, Xia, SM, Lu, X, Cai, F, Hwang, KK, Song, H, Zhou, T, Lynch, RM, Alam, SM, Moody, MA, Ferrari, G, Berrong, M, Kelsoe, G, Shaw, GM, Hahn, BH, Montefiori, DC, Kamanga, G, Cohen, MS, Hraber, P, Kwong, PD, Korber, BT, Mascola, JR, Kepler, TB, and Haynes, BF. "Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing antibodies." Cell 158, no. 3 (July 31, 2014): 481-491.
Horwitz, ME, Chao, NJ, Rizzieri, DA, Long, GD, Sullivan, KM, Gasparetto, C, Chute, JP, Morris, A, McDonald, C, Waters-Pick, B, Stiff, P, Wease, S, Peled, A, Snyder, D, Cohen, EG, Shoham, H, Landau, E, Friend, E, Peleg, I, Aschengrau, D, Yackoubov, D, Kurtzberg, J, and Peled, T. "Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment." The Journal of Clinical Investigation 124, no. 7 (July 2014): 3121-3128.
Doan, PL, Himburg, HA, Helms, K, Russell, JL, Fixsen, E, Quarmyne, M, Harris, JR, Deoliviera, D, Sullivan, JM, Chao, NJ, Kirsch, DG, and Chute, JP. "Epidermal growth factor regulates hematopoietic regeneration after radiation injury." Nat Med 19, no. 3 (March 2013): 295-304.
Liao, HX, Lynch, R, Zhou, T, Gao, F, Alam, SM, Boyd, SD, Fire, AZ, Roskin, KM, Schramm, CA, Zhang, Z, Zhu, J, Shapiro, L, Mullikin, JC, Gnanakaran, S, Hraber, P, Wiehe, K, Kelsoe, G, Yang, G, Xia, SM, Montefiori, DC, Parks, R, Lloyd, KE, Scearce, RM, Soderberg, KA, Cohen, M, Kamanga, G, Louder, MK, Tran, LM, Chen, Y, Cai, F, Chen, S, Moquin, S, Du, X, Joyce, MG, Srivatsan, S, Zhang, B, Zheng, A, Shaw, GM, Hahn, BH, Kepler, TB, Korber, BT, Kwong, PD, Mascola, JR, and Haynes, BF. "Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus." Nature 496, no. 7446 (April 3, 2013): 469-476. Open Access.
Conway, AE, Scotland, PB, Lavau, CP, and Wechsler, DS. "A CALM-derived nuclear export signal is essential for CALM-AF10-mediated leukemogenesis." Blood 121, no. 23 (June 6, 2013): 4758-4768.
Yoshizaki, A, Miyagaki, T, DiLillo, DJ, Matsushita, T, Horikawa, M, Kountikov, EI, Spolski, R, Poe, JC, Leonard, WJ, and Tedder, TF. "Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions." Nature 491, no. 7423 (November 8, 2012): 264-268.
Brennan, TV, Lin, L, Huang, X, Cardona, DM, Li, Z, Dredge, K, Chao, NJ, and Yang, Y. "Heparan sulfate, an endogenous TLR4 agonist, promotes acute GVHD after allogeneic stem cell transplantation." Blood 120, no. 14 (October 4, 2012): 2899-2908.
Coombs, CC, Rassenti, LZ, Falchi, L, Slager, SL, Strom, SS, Ferrajoli, A, Weinberg, JB, Kipps, TJ, and Lanasa, MC. "Single nucleotide polymorphisms and inherited risk of chronic lymphocytic leukemia among African Americans." Blood 120, no. 8 (August 23, 2012): 1687-1690.
Chen, DF, Prasad, VK, Broadwater, G, Reinsmoen, NL, DeOliveira, A, Clark, A, Sullivan, KM, Chute, JP, Horwitz, ME, Gasparetto, C, Long, GD, Yang, Y, Chao, NJ, and Rizzieri, DA. "Differential impact of inhibitory and activating Killer Ig-Like Receptors (KIR) on high-risk patients with myeloid and lymphoid malignancies undergoing reduced intensity transplantation from haploidentical related donors." Bone Marrow Transplant 47, no. 6 (June 2012): 817-823.
Himburg, HA, Muramoto, GG, Daher, P, Meadows, SK, Russell, JL, Doan, P, Chi, JT, Salter, AB, Lento, WE, Reya, T, Chao, NJ, and Chute, JP. "Pleiotrophin regulates the expansion and regeneration of hematopoietic stem cells." Nat Med 16, no. 4 (April 2010): 475-482.
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