Description of Research Expertise
Research in our laboratory is at the intersection of innate immune system and solid tumor biology. Specifically, we study the mononuclear phagocyte system (MPS) with an emphasis on their role in the tumor microenvironment. MPS is part of the innate immune system and comprises of monocytes, macrophages, and dendritic cells (DC). These cells are functionally, phenotypically, and developmentally heterogeneous with many distinct subsets. We are interested in understanding the molecular basis of this developmental and functional heterogeneity within the MPS. A major focus in our laboratory is to understand the role of MPS within the microenvironment of a group of solid tumors known as sarcomas. DCs and macrophages are thought to play important role in cancer by modulating host-immune responses against the tumor cells, promoting metastasis, angiogenesis, etc. Additionally, the ability of these cells to regulate lymphocyte function makes them an important determinant in the success of cancer immunotherapy. Using a combination of advanced genetically engineered mouse models in conjunction with patient-derived samples, we aim to uncover the molecular pathways underlying tumor-MPS interaction with the overarching goal of targeting them for therapeutic purposes.
Selected Publications
Ruth Choa, Junichiro Tohyama, Shogo Wada, Hu Meng, Jian Hu, Mariko Okumura, Rebecca M. May, Tanner F. Robertson1, Ruth-Anne Langan Pai1, Arben Nace, Christian Hopkins, Elizabeth A. Jacobsen, Malay Haldar, Garret A. FitzGerald, Edward M. Behrens, Andy J. Minn, Patrick Seale, George Cotsarelis, Brian Kim, John T. Seykora, Mingyao Li, Zoltan Arany, and Taku Kambayashi*: Thymic stromal lymphopoietin induces adipose loss through sebum hypersecretion. Science 373 (6554): eabd2893,2021.
Mai T. Dang, Michael Gonzalez, Krutika S. Gaonkar, Komal S. Rathi, PatriciaYoung, Sherjeel Arif, Li Zhai, Zahidul Alam, Samir Devalaraja, Tsun Ki To, Ian W. Folkert, Pichai Raman, Jo Lynne Rokita, Daniel Martinez, Jaclyn N. Taroni, Joshua Shapiro, Casey S. Greene, Candace Savonen, Hakon Hakonarson, Tom Curran, Malay Haldar: Macrophages in medulloblastoma display dynamic heterogeneity that vary with treatment modality Cell Reports
34 (13): 108917,2021.
Zahidul Alam, Samir Devalaraja, Minghong Li, Tsun Ki Jerrick To, Ian W. Folkert, Erick Mitchell-Velasquez, Mai T Dang, Patricia Young, Christopher J. Wilbur, Michael A. Silverman, Xinyuan Li, Youhai H. Chen, Paul Hernandez, Aritra Bhattacharyya, Mallar Bhattacharya, Matthew H. Levine, Malay Haldar.: Counter regulation of Spic by NF-κB and STAT signaling controls inflammation and iron metabolism in macrophages Cell Reports 31 (13): 107825,2020.
Samir Devalaraja, Tsun Ki Jerrick To, Ian W Folkert, Ramakrishnan Natesan, Md Zahidul Alam, Minghong Li, Yuma Tada, Konstantin Budagyan, Mai T Dang, Li Zhai, Graham P Lobel, Gabrielle E Ciotti, T S Karin Eisinger-Mathason, Irfan A Asangani, Kristy Weber, M Celeste Simon, Malay Haldar.: Tumor-Derived Retinoic Acid Regulates Intratumoral Monocyte Differentiation to Promote Immune Suppression Cell 180 (6): 1098-1114,2020.
Pek RH, Yuan X, Rietzschel N, Zhang J, Jackson L, Nishibori E, Ribeiro A, Simmons W, Jagadeesh J, Sugimoto H, Alam MZ, Garrett L, Haldar M, Ralle M, Phillips JD, Bodine DM, Hamza I.: Hemozoin produced by mammals confers heme tolerance. Elife 1 (8): doi: 10.7554/eLife.49503,2019.
Briseño CG*, Haldar M*, Kretzer NM, Wu X, Theisen DJ, Kc W, Durai V, Grajales-Reyes GE, Iwata A, Bagadia P, Murphy TL, Murphy KM.: Distinct Transcriptional Programs Control Cross-Priming in Classical and Monocyte-Derived Dendritic Cells Cell Reports 15 (11): 2462-2474,2016.
Haldar Malay, Kohyama Masako, So Alex Yick-Lun, Kc Wumesh, Wu Xiaodi, Briseño Carlos G, Satpathy Ansuman T, Kretzer Nicole M, Arase Hisashi, Rajasekaran Namakkal S, Wang Li, Egawa Takeshi, Igarashi Kazuhiko, Baltimore David, Murphy Theresa L, Murphy Kenneth M: Heme-mediated SPI-C induction promotes monocyte differentiation into iron-recycling macrophages. Cell 156 (6): 1223-34,2014.
Haldar Malay, Hedberg Matthew L, Hockin Matthew F, Capecchi Mario R: A CreER-based random induction strategy for modeling translocation-associated sarcomas in mice. Cancer research 69 (8): 3657-64,2009.
Haldar Malay, Hancock Jeffrey D, Coffin Cheryl M, Lessnick Stephen L, Capecchi Mario R: A conditional mouse model of synovial sarcoma: insights into a myogenic origin. Cancer cell 11 (4): 375-88,2007.
Haldar Malay, Karan Goutam, Tvrdik Petr, Capecchi Mario R: Two cell lineages, myf5 and myf5-independent, participate in mouse skeletal myogenesis. Developmental cell 14 (3): 437-45,2008.
Academic Contact Information
414 BRB II/III, 421 Curie Blvd
Philadelphia,
PA
19104
Phone: 215-573-9704