Ahmed Lab · Icahn School of Medicine at Mount Sinai
A chimeric receptor changes more than a T cell’s specificity — it changes how it interacts with other immune cells as well. We study that re-wiring.
Our discovery
Dendritic cells dress in tumor antigen. We can leverage that.
No current strategy can selectively boost CAR T cell activity at the tumor site without also driving toxicity elsewhere. We found one.
After focal radiation, dendritic cells at the tumor acquire tumor antigens on their surface and directly expand CAR T cells through a chimeric synapse. The effect is local: CAR T cells persist and kill at the irradiated site, while systemic activity stays in check. The therapeutic window widens — enough to control extensive, radioresistant disease in our preclinical models.
A dendritic cell (CD11c+ light blue) dressed in tumor target antigen (yellow).
How we think
The target determines the fate of the effector.
A T cell engineered to recognize a B cell antigen expands and persists. The same T cell engineered against a solid tumor antigen often does neither. The difference isn’t only the tumor — it’s the new set of immune interactions the chimeric receptor pulls the T cell into.
Our lab works in that re-wiring. We use immunocompetent mouse models, in vivo CRISPR screens, and CAR T engineering to map how chimeric receptors impact T cell interactions with immune cells in the TME — and to turn those interactions into therapy.
Principal Investigator
Jalal Ahmed
Assistant Professor,
Icahn School of Medicine
at Mount Sinai
Biosketch
Icahn School of Medicine at Mount Sinai — Assistant Professor, Immunology & Immunotherapy / Radiation Oncology
New York, NY
Icahn School of Medicine at Mount Sinai — Resident, Radiation Oncology
New York, NY · B. Leonard Holman Research Pathway
Northwell Health — Resident, Internal Medicine
Manhasset, NY
Icahn School of Medicine at Mount Sinai — MD/PhD, MSTP Dual Degree Program
New York, NY · PhD: Development and Stem Cell Biology, Immunology
Icahn School of Medicine at Mount Sinai — Post-Baccalaureate Research Education Program
New York, NY
Columbia University — BS, Biomedical Engineering
New York, NY
Awards & Honors
NIH Director’s Early Independence Award (DP5), National Institutes of Health, 2021
Young Investigator Award, ASCO / Conquer Cancer Foundation, 2019
Scientific Award, Lung Cancer Research Foundation, 2018
B. Leonard Holman Research Pathway, American Board of Radiology, 2018
Student Speaker Award, 213th Meeting, Interurban Clinical Club, 2016
F30 Ruth L. Kirschstein NRSA Individual Predoctoral MD/PhD Award, NIH, 2014
New Investigator Student Award, 43rd Meeting, Society for Experimental Hematology, 2014
Pharmacology Training Grant (T32), National Institutes of Health, 2010
Research
Research Focus
We pursue four interconnected research areas, united by the goal of making CAR T cell therapy effective against solid tumors. The Jalal Ahmed Lab is part of the Precision Immunology Institute and the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai.
We seek to:
- 1Identify how chimeric receptors alter T cell immunobiology within the immune TME
- 2Understand how radiotherapy can reshape the tumor immune landscape and improve CAR T cell therapy
- 3Develop novel cell therapies that capitalize on CAR T cell immunology in the TME
Targeting the Tumor Microenvironment to Advance CAR T Therapy
We develop novel strategies to reprogram the immunosuppressive tumor microenvironment — with a particular focus on myeloid cells — to overcome resistance and enhance the efficacy of CAR T cell therapy in solid tumors.
Myeloid Cell Biology and Immunosuppression in Cancer
Investigating how tumor-associated macrophages and myeloid-derived suppressor cells regulate anti-tumor immunity and identifying therapeutic targets to restore immune responsiveness.
Widening the Therapeutic Window to Control Advanced Solid Tumor
Leveraging radiation-induced immunomodulation to reshape the tumor microenvironment and improve CAR T cell infiltration, persistence, and anti-tumor activity.
Engineering Next-Generation CAR T Cells for Solid Tumors
Designing advanced CAR constructs and delivery approaches that enable better penetration, durability, and function in the hostile solid tumor setting.
Publications
Selected Publications
bold = Ahmed lab members / † = corresponding/co-corresponding / * = equal contribution
Please contact Jalal directly if paywalls get in your way!
Proceedings of the National Cancer Institute Workshop on combining immunotherapy with radiotherapy: challenges and opportunities for clinical translation
Morris ZS, Demaria S, Monjazeb AM, Formenti SC, Weichselbaum RR, Welsh J, Enderling H, Schoenfeld JD, Brody JD, McGee HM, Mondini M, Kent MS, Young KH, Galluzzi L, Karam SD, Theelen WSME, Chang JY, Huynh MA, Daib A, Pitroda S, Chung C, Serre R, Grassberger C, Deng J, Sodji QH, Nguyen AT, Patel RB, Krebs S, Kalbasi A, Kerr C, Vanpouille-Box C, Vick L, Aguilera TA, Ong IM, Herrera F, Menon H, Smart D, Ahmed J, Gartrell RD, Roland CL, Fekrmandi F, Chakraborty B, Bent EH, Berg TJ, Hutson A, Khleif S, Sikora AG, Fong L
Lancet Oncol. 26(3), e152-e170
Dendritic cells type 1 control the formation, maintenance, and function of tertiary lymphoid structures in cancer
Mattiuz R, Boumelha J, Hamon P, Le Berichel J, Vaidya A, Soong B, Halasz L, Radkevich E, Kim H, Park M, Donne R, Troncoso L, D’Souza D, Kaiza M, MacFawn I, Belabed M, Mestrallet G, Humblin E, Merand R, Hennequin C, Ioannou G, Ozbey S, Figueiredo I, Hegde S, Tepper A, Merarda H, Nemeth E, Goldstein S, Reid A, Noureddine M, Tabachnikova A, Ahmed J, Polydorides A, Bhardwaj N, Lujambio A, Chen Z, Gonzalez Kozlova E, Kim-Schulze S, Brody J, Schotsaert M, Merad M†
bioRxiv
Dendritic cells accelerate CAR T cells in irradiated tumors through chimeric synapses
Navarre S*, Ishibashi M*, Nair A*, Reyes-Torres I, Belabed M, Halasz L, Park M, Mattiuz R, Ounadjela M, Gunset G, Mansilla-Soto J, Feucht J, Cabriolu A, Berichel J, Eyquem J, Brown B, Merad M, Sadelain M†, Ahmed J†
bioRxiv
Targeting Macrophages with CAR T Cells Delays Solid Tumor Progression and Enhances Antitumor Immunity
Sánchez-Paulete AR, Mateus-Tique J, Mollaoglu G, Nielsen SR, Marks A, Lakshmi A, Khan JA, Wilk CM, Pia L, Baccarini A, Merad M, Brown BD†
Cancer Immunol Res. 10(11), 1354-1369
Pathologic Angiogenesis of Malignant Vascular Sarcomas: Implications for Treatment
Khan JA*†, Maki RG, Ravi V
J Clin Oncol. 36(2), 194-201
Published under the pen name Ahmed-Khan
Fetal liver hematopoietic stem cell niches associate with portal vessels
Khan JA*, Mendelson A, Kunisaki Y, Birbrair A, Kou Y, Arnal-Estapé A, Pinho S, Ciero P, Nakahara F, Ma’ayan A, Bergman A, Merad M, Frenette PS†
Science 351(6269), 176-80
Published under the pen name Ahmed-Khan
Megakaryocytes regulate hematopoietic stem cell quiescence through CXCL4 secretion
Bruns I*, Lucas D, Pinho S, Ahmed J, Lambert MP, Kunisaki Y, Scheiermann C, Schiff L, Poncz M, Bergman A, Frenette PS†
Nat Med. 20(11), 1315-20
Osterix marks distinct waves of primitive and definitive stromal progenitors during bone marrow development
Mizoguchi T*, Pinho S, Ahmed J, Kunisaki Y, Hanoun M, Mendelson A, Ono N, Kronenberg HM, Frenette PS†
Dev Cell 29(3), 340-9
Arteriolar niches maintain haematopoietic stem cell quiescence
Kunisaki Y*, Bruns I*, Scheiermann C*, Ahmed J*, Pinho S, Zhang D, Mizoguchi T, Wei Q, Lucas D, Ito K, Mar JC, Bergman A, Frenette PS†
Nature 502(7473), 637-43
Team
Team
Current Members
Xiaomei Yang
Staff Scientist
Xiaomei is a staff scientist in the Ahmed Lab contributing to the development of novel CAR T cell strategies and investigation of the tumor immune microenvironment.
Hao Zheng
Graduate Student
Hao is a graduate student working on understanding the interplay between myeloid cells and engineered T cells in solid tumors.
Alumni
Sophia Navarre
Research Technician (2022–2025) — Now PhD Candidate in Biomedical Engineering at CUNY.
Maki Ishibashi
Research Technician (2023–2025) — Now pursuing MD/PhD training in cancer immunology.
Oscar Padilla, MD
Research Fellow (2022–2023) — Now Assistant Professor of Radiation Oncology at Mount Sinai.
Achuth Nair, BS
Research Technician (2020–2022) — Now PhD Candidate at Gerstner Sloan Kettering Graduate School, MSKCC.
Merouane Ounadjela, BS
Research Technician (2019–2020)
Janaki Nair
Research Intern (2022) — Now at Columbia College.
Contact
Get in Touch
Location
Icahn School of Medicine at Mount Sinai
Hess Center for Science and Medicine
Department of Radiation Oncology
Precision Immunology Institute
1470 Madison Avenue
New York, NY 10029
Inquiries
For scientific inquiries, collaborations, or interest in joining the lab:
jalal.ahmed{@}mountsinai.org
For administrative and scheduling inquiries:
Morgan Pierce
morgan.pierce{@}mountsinai.org
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Supported By
We are grateful for the generous support of our funding agencies, whose investment makes this research possible.