Samarth Hegde, M.S., Ph.D.

Our laboratory of Reactive Myeloid Cell Biology is passionate about understanding how certain immune cells—monocytes and neutrophils—get co-opted by malignant cells to weaken the body’s natural defenses against cancer. We are particularly interested in how these immune cells are molded and educated by systemic inflammation during their ‘birth’ in places like the bone marrow and spleen, setting the stage for immunosuppression and pathological behavior. We also study how the development of these immune cells is imprinted by cancer treatments like chemotherapy and radiation, which can place stress on the immune system and distort their function.

By combining detailed studies of patient samples over time with mechanistic experiments in mouse models, we aim to uncover how inflammation rewires these myeloid-lineage cells at multiple levels—affecting how their genes are regulated, how they interact with their surroundings, and how they use or shuttle metabolites. Ultimately, our goal is to use these insights to design better myeloid cell-targeted treatments for cancers such as pancreatic cancer, working closely with clinical collaborators at Einstein and beyond.

Some of the key questions we are exploring:

How does cancer-driven systemic inflammation change myeloid cells at their source?
Our previous work shows that tumors can alter how early immune cells are programmed far away in the bone marrow and spleen. We are now digging deeper into how these changes happen, how long they last, and which genes are most affected. To do this, we use advanced omics-based tools in reporter mouse models and primary human samples, that allow us to study gene activity and regulation in great detail.

How does cancer inflammation affect the metabolism of developing myeloid cells?
Tumor signals can disrupt the normal balance within the bone marrow stem cell niche, increasing cellular oxidative stress and interfering with how proteins are made and maintained (proteostasis). We study how these cues can affect quiescence, differentiation, and fate of myeloid-biased stem cells and progenitors, especially by altering key organelles like the endoplasmic reticulum and mitochondria.

How do cancer treatments rewire our ‘reactive’ immune system?
Treatments like chemotherapy and radiation can severely strain the bone marrow and temporarily weaken immune function, followed often by a myeloid cell-driven ‘rebound’. We are interested in delineating both the short-term effects (when the immune system is suppressed) and the long-term consequences (when it “remembers” this suppression phase). This work has important implications for clinical care in the context of recovery post-therapy, susceptibility to infection, and risk for secondary neoplasms.

Do treatment-driven immune changes affect cancer spread or relapse?
After many cancer treatments, the host immune system rebounds by producing large numbers of new myeloid cells. While this helps recovery, it may also unintentionally support cancer cells—either by helping them spread (metastatic growth) or by “waking up” cancer cells that had been quiescent (dormancy exit). Within the larger Cancer Dormancy Institute, we are studying this delicate interplay between myeloid rebound and subsequent metastatic/relapse risk. The translational goal is to develop myeloid-targeting strategies that complement existing therapies, limit long-term relapse/metastatic risk, while sparing homeostatic function.

1. Hegde S, Giotti B^, Soong BY^, Halasz L, Le Berichel J, Schaefer MM, Kloeckner B, Mattiuz R, Park MD, Magen A, Marks A, Belabed M, Hamon P, …, Kim-Schulze S, Flores RM, Kaufman AJ, Ginhoux F, Buenrostro JD, Josefowicz SZ, Tsankov AM, Marron TU, Ma S, Brown BD, Merad M. Myeloid progenitor dysregulation fuels immunosuppressive macrophages in tumours. Nature. 2025 Sep 10. doi: 10.1038/s41586-025-09493-y. Epub ahead of print. PMID: 40931076
2. Park MD, Le Berichel J, Hamon P, Wilk CM, Belabed M, Yatim N, Saffon A, Boumelha J, Falcomatà C, Tepper A, Hegde S, … Vabret N, Brown BD, Marron TU, Merad M. Hematopoietic aging promotes cancer by fueling IL-1⍺-driven emergency myelopoiesis. Science. 2024 Sep 5:eadn0327. doi: 10.1126/science.adn0327. PMID: 39236155
3. LaMarche NM, Hegde S^, Park MD^, Maier BB, Troncoso L, Le Berichel J, Hamon P, Belabed M,… Passegué E, Kim-Schulze S, Brown BD, Hirsch FR, Kim BS, Marron TU, Merad M. An IL-4 signalling axis in bone marrow drives pro-tumorigenic myelopoiesis. Nature. 2023 Dec 6. doi: 10.1038/s41586-023-06797-9. PMID: 38057662
4. Park MD*, Reyes-Torres I*, LeBerichel J, Hamon P, LaMarche NM, Hegde S, Belabed M,…Colonna M, Marron TU, Merad M. TREM2 macrophages drive NK cell paucity and dysfunction in lung cancer. Nature Immunology. 2023 May;24(5):792-801. doi: 10.1038/s41590-023-01475-4. Epub 2023 Apr 20. PMID: 37081148
5. Hegde S, Krisnawan VE, Herzog BH, Zuo C, Breden MA, Knolhoff BL, Hogg GD, Tang JP, Baer JM, Mpoy C, Lee KB, Alexander KA, Rogers BE, Murphy KM, Hawkins WG, Fields RC, DeSelm CJ, Schwarz JK, DeNardo DG. (2020) Dendritic Cell Paucity Leads to Dysfunctional Immune Surveillance in Pancreatic Cancer. Cancer Cell; Mar 16 2020. PMID: 32183949
6. Jiang H, Hegde S, Knolhoff BL, Zhu Y, Herndon JM, Meyer MA, Nywening TM, Hawkins WG, Shapiro IM, Weaver DT, Pachter JA, Wang-Gillam A, DeNardo DG. (2016). Targeting Focal Adhesion Kinase Renders Pancreatic Cancers Responsive to Checkpoint Immunotherapy. Nature Medicine; July 4 2016. PMID: 27376576

Selected Reviews:

1. Park MD, Belabed M, Chen ST, Hamon P, Hegde S, … Merad, M. (2023) On the Biology and Therapeutic Modulation of Macrophages and Dendritic Cells in Cancer. Annual Reviews of Cancer Biology Vol. 7:291-311 April 2023 [Review]
2. Hegde S*, Leader AM*, Merad M. (2021) MDSC: Markers, development, states, and unaddressed complexity. Immunity. 2021 May 11. [Review] PMID: 33979585    *co-first author
3. Hegde S. (2020) Pancreatic Cancer Immuno-oncology in the Era of Precision Medicine. Indian Journal of Surgical Oncology; Aug 2020, 1-10. [Review] PMID: 33994737
4. Vabret N, Britton GJ, Gruber C, Hegde S, Kim J,…Samstein RM, Sinai Immunology Review Project. Immunology of COVID-19: current state of the science. Immunity; May 5 2020. [Review] PMID: 32505227
5. Jiang H, Hegde S, DeNardo DG. (2017) Tumor-associated fibrosis as a regulator of tumor immunity and response to immunotherapy. Cancer Immunology Immunotherapy; 1-12. [Review] PMID: 28451791

A complete list of our publications can be found at myNCBI or Google Scholar.