Our Research

In the last decade, researchers have identified key genetic events that characterize MDS. These cellular and molecular findings can help with disease prognosis, however, how the disease arises and progresses remains unknown and therapies lag behind research. Modern standard of care therapies either aim to boost the defective blood cell production in the bone marrow, or to treat the underlying MDS cell of origin using drugs that inhibit DNA methylation, suppressing rapid cell growth associated with MDS. Unfortunately, most MDS patients still succumb from the defect in blood production associated with the bone marrow failure as a consequence of MDS. In addition, in more than 30% percent of MDS patients, the disease evolves to an aggressive acute myeloid leukemia (AML). These patients often are left with a poor prognosis of MDS and transformed AML that is resistant to chemotherapy and in majority older patients, unable to go through allogeneic stem cell transplant. Targeted therapies from novel and exciting discoveries that are intrinsic to the MDS cell have also very limited potency when tried in MDS patients due to how the disease adapts to evade therapies mainly by generating MDS cells with new mutations.

Publications

Ali, A.M., Burke, A., Borot, F., Du, X. Mukherjee, S., et al. A novel therapeutic bispecific format based on synthetic orthogonal heterodimers enables T cell activity against Acute myeloid leukemia. Oncogene (2022). https://doi.org/10.1038/s41388-022-02532-2

Galán-Díez M, Borot F, Ali AM, Zhao J, Gil-Iturbe E, Shan X, Luo N, Liu Y, Huang XP, Bisikirska B, Labella R, Kurland I, Roth BL, Quick M, Mukherjee S, Rabadán R, Carroll M, Raza A, Kousteni S. Subversion of Serotonin Receptor Signaling in Osteoblasts by Kynurenine Drives Acute Myeloid Leukemia. Cancer Discov. 2022 Apr 1;12(4):1106-1127. doi: 10.1158/2159-8290.CD-21-0692. PMID: 35046097; PMCID: PMC8983599.

Meron E, Thaysen M, Angeli S, Antebi A, Barzilai N, Baur JA, Bekker-Jensen S, Birkisdottir M, Bischof E, Bruening J, Brunet A, Buchwalter A, Cabreiro F, Cai S, Chen BH, Ermolaeva M, Ewald CY, Ferrucci L, Florian MC, Fortney K, Freund A, Georgievskaya A, Gladyshev VN, Glass D, Golato T, Gorbunova V, Hoejimakers J, Houtkooper RH, Jager S, Jaksch F, Janssens G, Jensen MB, Kaeberlein M, Karsenty G, de Keizer P, Kennedy B, Kirkland JL, Kjaer M, Kroemer G, Lee KF, Lemaitre JM, Liaskos D, Longo VD, Lu YX, MacArthur MR, Maier AB, Manakanatas C, Mitchell SJ, Moskalev A, Niedernhofer L, Ozerov I, Partridge L, Passegué E, Petr MA, Peyer J, Radenkovic D, Rando TA, Rattan S, Riedel CG, Rudolph L, Ai R, Serrano M, Schumacher B, Sinclair DA, Smith R, Suh Y, Taub P, Trapp A, Trendelenburg AU, Valenzano DR, Verburgh K, Verdin E, Vijg J, Westendorp RGJ, Zonari A, Bakula D, Zhavoronkov A, Scheibye-Knudsen M. Meeting Report: Aging Research and Drug Discovery. Aging (Albany NY). 2022 Jan 28;14(2):530-543. doi: 10.18632/aging.203859. Epub 2022 Jan 28.PMID: 35089871 Free PMC article.

Mitchell, Carl A., et al. “Stromal Niche Inflammation Mediated by IL-1 Signalling Is a Targetable Driver of Haematopoietic Ageing.” Nature Cell Biology, vol. 25, no. 1, 2023, pp. 30–41., https://doi.org/10.1038/s41556-022-01053-0

Mukherjee, S., Ali, A.M., Murty, V.V., A. Raza. et al. Mutation in SF3B1 gene promotes formation of polyploid giant cells in Leukemia cells. Med Oncol 39, 65 (2022).

Valet C, Magnen M, Qiu L, Cleary SJ, Wang KM, Ranucci S, Grockowiak E, Boudra R, Conrad C, Seo Y, Calabrese DR, Greenland JR, Leavitt AD, Passegué E, Mendez-Ferrer S, Swirski FK, Looney MR.J. Sepsis promotes splenic production of a protective platelet pool with high CD40 ligand expression. Clin Invest. 2022 Feb 22:e153920. doi: 10.1172/JCI153920. Online ahead of print.PMID: 35192546 Free article.

Our Approach

The Edward P. Evans Center for Myelodysplastic Syndromes (MDS) at Columbia University aims to use the knowledge obtained from our holistic and multidisciplinary approach to develop new and innovative therapies that target the MDS cell directly but also cells in its bone marrow environment that promote its growth. We will leverage:

A multidisciplinary collaborative team that brings together the breadth of expertise of CUIMC faculty in basic, translational and clinical research. It includes investigators with committed MDS research programs combining expertise in human genetics, bench-to-bed-side translation of research findings, patient treatment, generation and use of genetically modified mouse models and unique expertise in the role of the bone marrow microenvironment in MDS. It also includes scientists who will be redirecting research from other relevant areas to apply to MDS; specifically, biology of aging, inflammatory stress, tumor initiation, RNA biology and experimental therapeutics in lymphoma.

An MDS sample repository of more than 60,000 samples from thousands of unique MDS patients studied longitudinally over the natural history of their disease built by Dr. Raza in a program initiated in 1984.

A therapeutic effort dedicated to harness the work of our scientists to develop new therapeutics for MDS. This includes targeting genetic, epigenetic, and cellular events that promote MDS growth as well as approaches that target MDS-initiating or propagating signals from cells in the bone marrow microenvironment as a means to achieve a more durable efficacy.

A technical innovation arm to leverage technologies developed by members of our team and others offered at CUIMC, Herbert Irving Comprehensive cancer center (HICCC), and Cores, including single cell genomics, transcriptomics and epigenomics to study cellular heterogeneity, genetic CRISPR screens to identify and validate disease drivers and actionable targets.