Chozha Rathinam, Dr. rer. nat.

Dr. Rathinam completed his doctoral (Dr. rer. nat./ Ph.D.) studies at the Hannover Medical School, Germany. Dr. Rathinam's doctoral work unraveled  the key role of the transcription factor-Gfi1 in the differentiation of dendritic cells from Hematopoietic Stem Cells (HSCs) (Rathinam, Immunity, 2005; Rathinam, Leukemia, 2006).

During his postdoctoral studies, in the laboratory of Dr. Richard Flavell, Yale University School of Medicine, New Haven, CT, Dr. Rathinam discovered the previously unappreciated, but physiologically significantly, roles of post-translational modifications  (Ubiquitylation) of proteins in the maintenance of HSCs  (Rathinam, Genes & Development, 2008;Rathinam, Proc Natl Acad Sci USA, 2010,  Rathinam, Nature Immunology, 2011) and transformation of normal stem cells into Leukemic Stem Cells (Rathinam, Cancer Cell, 2010).  Of note, this work was recognized as the “novel avenue of stem cell biology” by the experts in the field.  

In addition, Dr. Rathinam generated  and studied a novel line of humanized knock-in mouse model that expresses key human hematopoietic cytokines. Dr. Rathinam’s seminal work  on  this unique ‘humanized’ mouse model revealed a superior engraftment  of Human HSCs and efficient differentiation of human immune system, especially towards the human macrophage lineage,  under Xenogeneic settings (Rathinam, Blood, 2011).  

In 2010, Dr. Rathinam served as a group leader at the NIH center for excellence in Stem Cell Biology, Providence, RI.  

In 2011, Dr. Rathinam became an Assistant Professor at the Department of Genetics & Development, Columbia University Medical Center, New York, NY.  

In  2016, Dr. Rathinam joined the Institute of Human Virology, University of Maryland School of Medicine, Baltimore.

In 2025, Dr. Rathinam became a faculty member of Program in Oncology, Marlene & Stewart Greenebaum Comprehensive Cancer Center.

For almost two decades, research in Dr. Rathinam’s laboratory has been focusing  on major intrinsic and extrinsic molecular circuits that cause cancer, stem cell defects, inflammatory disorders, immunodeficiencies and aging.  

Stem Cells, Dendritic cells, Inflammation, Autoimmunity, Neuroinflammation, & HIV-induced hematopathology and immunodeficiencies.

1. Silvestri G and Rathinam CV. Trim28 plays an indispensable role in maintaining functions and transcriptional integrity of hematopoietic stem cells.  bioRxiv.  https://doi.org/10.1101/2022.07.12.499765

2. Tsymbalyuk O, Gerzanich V, Simard M and Rathinam CV. Traumatic brain injury alters dendritic cell differentiation and distribution in lymphoid and non-lymphoid organs.   Journal of Neuroinflammation 19, 238 (2022)

3. Thummar, K. and Rathinam, CV. Class I PI3K regulatory subunits control differentiation of dendritic cell subsets and regulate Flt3L mediated signal transduction. Scientific Reports 12(1): 12311 (2022).

4. Lakhan R and Rathinam CV.  Deficiency of Rbpj Leads to Defective Stress-Induced Hematopoietic Stem Cell Functions and Hif Mediated Activation of Non-canonical Notch Signaling Pathways. Front Cell Dev Biol.8 (2021).

5. Nakagawa MM and Rathinam CV. A20 deficiency in hematopoietic stem cells causes lymphopenia and myeloproliferation due to elevated Interferon-γ signals. Scientific Reports 9, 12658 (2019).

6. Nakagawa M and Rathinam CV. Constitutive activation of the canonical NF-κB pathway leads to progressive Bone Marrow Failure and induction of Erythroid Transcriptional Program in Hematopoietic Stem Cells. Cell Reports 25, 2094-2109 (2018).

7. Nakagawa MM, Chen H and Rathinam CV. Constitutive activation of NF-kB pathway in hematopoietic stem cells causes loss of quiescence and deregulated transcription factor networks. Frontiers in Cell and Developmental Biology 6, 143 (2018).

8. Nakagawa M, Davis H and  Rathinam CV. A20 deficiency in Multipotent Progenitors perturbs quiescence of Hematopoietic Stem Cells. Stem Cell Research 33:199-205 (2018).

9. Lu K, Nakagawa MM, Thummar K and Rathinam CV. The Slicer Endonuclease Argonaute 2 is a Negative Regulator of Hematopoietic Stem Cell Quiescence. Stem Cells 34,1343-53 (2016).

10. Nakagawa MM, Thummar K, Mandelbaum J, Pasqualucci L and Rathinam CV. Lack of the Ubiquitin-Editing Enzyme A20 results in loss of Hematopoietic Stem Cell Quiescence. The Journal of Experimental Medicine 212, 203-16 (2015)

11. Rathinam CV. The 'Inflammatory' control of hematopoietic stem cells. Oncotarget 6,19938-9 (2015)

12. Rathinam CV, Majetic L and Flavell R. The HECT domain E3 ligase Itch negatively controls haematopoietic stem cell maintenance and functions. Nature Immunology 12, 399-407 (2011)

13. Rathinam CV, Thien C, Flavell Rand Langdon W. Myeloid leukemia development in c-Cbl RING finger mutant mice is dependent on FLT3 signaling. Cancer Cell 18, 341-52 (2010)

14. Rathinam CV, Thien C, Langdon W, Gu H, Flavell R. The E3 ubiquitin ligase c-Cbl restricts development and functions of hematopoietic stem cells. Genes &  Development 22, 992-997 (2008).

15. Rathinam CV, Geffers R, Yücel R, Buer J, Welte K, Möröy T, Klein C. The transcriptional repressor Gfi1 controls STAT3-dependent dendritic cell development and –function. Immunity 22, 717-728 (2005).

21. De A, Dainichi T, Rathinam CV and Ghosh S.The deubiquitinase activity of A20 is dispensable for NF-κB signaling. EMBO Reports15, 775-83 (2014).

22. Kode A, Manavalan JS, Mosialou I, Bhagat G, Rathinam CV, Luo N, Khiabanian H, Lee A, Murty VV, Friedman R, Brum A, Park D, Galili N, Mukherjee S, Teruya-Feldstein J, Raza A, Rabadan R, Berman E and Kousteni S. Leukaemogenesis induced by an activating β-catenin mutation in osteoblasts. Nature 506, 240-4 (2014).

23. Baldzizhar R, Fedorchuk C, Jha M, Rathinam CV, Henegariu O and Czyzyk J. Anti-serpin antibody mediated regulation of proteases in autoimmune diabetes. The Journal  of Biological Chemistry 288, 1612-9 (2013).

24. Kriegel MA, Rathinam CV and Flavell RA.Pancreatic Islet expression of Chemokine CCL2 suppresses autoimmune diabetes via tolerogenic CD11C+CD11B+ Dendritic Cells. Proc Natl Acad Sci USA 109, 3457-62 (2012).

25. Ahmed N, Zeng M, Sinha I, Polin L, Wei WZ, Rathinam CV, Flavell R, Massoumi R and Venuprasad K. The E3 Ligase Itch and Deubiquitinase Cyld act together to regulate Tak1 and Inflammation. Nature Immunology, 12, 1176-83 (2011).

26. Rathinam CV, PoueymirouWT, RojasJ, MurphyAJ, ValenzuelaDM, YancopoulosGD, Rongvaux A, EynonEE, Manz  MG and FlavellRA. Efficient differentiation and functions of human macrophages in the humanized M-CSF mice. Blood 118, 3119-28 (2011).

27. Strowig T, Rongvaux A, Rathinam CV, Eynon EE, Manz MG and Flavell RA. Transgenic expression of human SIRPa improves the engraftment of human cells in Rag2-/- common gC-/- mice. Proc Natl Acad Sci USA 108, 13218-23 (2011).

28. Kamanaka M, Zenewicz LA, Huber S, Gagliani N, Rathinam CV,  O’ Connor W, Wan YY, Nakae S, Iwakura Y, Hao L and Flavell R. CD45RB^lo CD4 T cells are controlled directly by IL-10 and cause IL-22 dependent colitis. The Journal of Experimental Medicine 208,1027-40 (2011).

29. Rongvaux A, Willinger T, Takizawa H, Rathinam CV, Wojtek A, Murphy AJ, Valenzuela DM, Yancopoulos GD, Eynon EE, Stevens S, Manz MG and Flavell RA. Human thrombopoietin Knock-in mice efficiently support human hematopoietic stem and progenitor cells. Proc Natl Acad Sci USA 108, 2378-83 (2011).

30. Rathinam CV and Flavell R. c-Cbl deficiency leads to diminished lymphocyte development and functions. Proc Natl Acad Sci USA107, 8316-21 (2010).

31.RathinamCV*, KriegelM* and FlavellR. E3 Ubiquitin Ligase GRAIL Controls Primary T Cell Activation and Oral Tolerance. Proc Natl Acad Sci USA 106, 16770-5 (2009). *Equal contribution & Indicated First

32. Legrand N, Ploss A, Balling R, Becker PD, Borsotti C, Brezillon N, Debarry J, de Jong Y, Deng H, Di Santo JP, Eisenbarth S, Eynon E, Flavell RA, Guzman CA, Huntington ND, Kremsdorf D, Manns MP, Manz MG, Mention JJ, Ott M, Rathinam C, Rice CM, Rongvaux A, Stevens S, Spits H, Strick-Marchand H, Takizawa H, van Lent AU, Wang C, Weijer K, Willinger T, Ziegler P. Humanized mice for modeling human infectious disease: challenges, progress, and outlook Cell Host Microbe 6, 5-9  (2009)

33. Rathinam CV*, Schwermann J*, Schubert M*, Schumacher S, Noyan F, Koseki H,  Kotlyarov A, Klein C, Gaestel M. MAPKAP Kinase MK2 maintains self-renewal capacity of hematopoietic stem cells. The EMBO Journal 28, 1392-406 (2009). *Equal contribution & Indicated First

34. Templin C, Kotlarz D, Rathinam CV, Rudolph C, Schätzlein S, Ramireddy K,    Rudolph KL, Schlegelberger B, Klein C, Drexler H.Establishment of immortalized multipotent hematopoietic progenitor cell lines by retroviral-mediated gene transfer of beta-catenin. Experimental Hematology 36, 204-15 (2008).

35. Rathinam CV and Flavell R. The hematopoiesis paradigm: clarity or ambiguity ? Blood 112, 3534-5 (2008).

36. Ju Z, Jiang H, Jaworski M, Rathinam CV, Gompf A, Klein C, Trumpp A, and Rudolph KL. Telomere dysfunction induces environmental alterations limiting hematopoietic stem cell function and engraftment. Nature Medicine13, 742-747 (2007).

37. Klein C, Grudzien M, Appaswamy G, Germeshausen M, Sandrock I, Schäffer AA, Rathinam CV, Boztug K, Schwinzer B, Rezaei N, Bohn G, Melin M, Carlsson G, Fadeel B, Dahl N, Palmblad J, Henter JI, Zeidler C, Grimbacher B, Welte K. Hax1 deficeincy causes autosomal recessive severe congenital neutropenia (Kostmann disease). Nature Genetics 39, 86-92 (2007).

38. Bohn G, Allroth A, Brandes G, Thiel J, Glocker E, Schaffer AA, Rathinam CV, Taub N, Teis D, Zeidler C, Dewey RA, Geffers R, Buer J, Huber LA, Welte K, Grimbacher B, Klein C. A novel human primary immunodeficiency syndrome caused by deficiency of the endosomal adaptor protein p14. Nature Medicine 13, 38-45 (2007).

39. Jung J, Bohn G, Allroth A, Boztug K, Brandes G, Sandrock I, Schaffer AA, Rathinam CV, Kollner I, Beger C, Schilke R, Welte K, Grimbacher B, Klein C. Identification of a homozygous deletion in the AP3B1 gene causing Hermansky-Pudlak syndrome, type 2. Blood 108, 362-9 (2006).

40. Rathinam CV, Sauer M, Ghosh A, Rudolph C, Hegazy A, Schlegelberger B, Welte K, Klein C. Generation and characterisation of a novel hematopoietic progenitor cell line with DC differentiation potential. Leukemia 20, 870-6 (2006).

41. Saravanamuthu SS, von Gotz F, Salunkhe P,  Rathinam CV, Geffers R, Buer J,Tummler B, Steinmetz I.Evidence for polyadenylated mRNA in Pseudomonas aeruginosa. Journal of Bacteriology 186, 7015-8 (2004).

42. Krishnamurthy KVK , Krishnaraj R, Rathinam CV, Christopher S. The Programme Of Cell Death In Plants and Animals -A Comparison. Current Science 79 (2000).

For almost two decades, research in the Rathinam Laboratory at Columbia University and the University of Maryland has elucidated fundamental mechanisms by which inflammatory signaling regulates immune homeostasis and cancer development. Our work has established critical roles for the NF-κB pathway regulators A20 and IKK2 in controlling innate and adaptive immune responses, hematopoietic homeostasis, and inflammatory circuits, revealing how their dysregulation promotes tumor initiation, immune evasion, stem cell dysfunction, and chronic inflammatory disease. Building on this foundation, our current research focuses on understanding how chronic inflammation and immune defects reshape the tumor microenvironment to suppress anti-tumor immunity. We are particularly interested in defining the molecular mechanisms that impair dendritic cell function, promote immunosuppressive myeloid cell programming, and drive resistance to cancer immunotherapy. Our long-term goal is to leverage these mechanistic insights to develop next-generation immunotherapies that restore productive anti-tumor immune responses and improve clinical outcomes for patients with cancer.

The major lines of our current investigation include:

1. Unraveling the HIV–Cancer Axis: While ART has substantially reduced the incidence of AIDS-defining malignancies, the burden of non-AIDS-defining cancers—including Lung cancer, Anal cancer, Hepatocellular carcinoma, and Hodgkin lymphoma—continues to rise. Importantly, these cancers often exhibit more aggressive clinical behavior and poorer outcomes in people living with HIV than in the general population. Chronic immune activation, persistent inflammation, incomplete immune restoration despite viral suppression, and co-infections with oncogenic viruses collectively contribute to an immunological environment that promotes tumor development. However, the cellular and molecular mechanisms by which chronic HIV-associated inflammation reshapes the tumor immune microenvironment and impairs anti-tumor immunity remain poorly understood. To this end, research in our laboratory aims to identify the immunological mechanisms linking chronic HIV infection and cancer to develop novel therapeutic strategies that restore anti-tumor immunity.

2. Engineering Next-Generation Dendritic Cell-based Immunotherapies for Cancer: Dendritic cells (DCs) are the principal antigen-presenting cells that initiate and sustain anti-tumor immunity by capturing, processing, and cross-presenting tumor antigens to activate tumor-specific T cells. Although DC-based immunotherapy has demonstrated considerable promise, its efficacy against most solid tumors remains limited because the tumor microenvironment suppresses DC maturation, antigen presentation, migration, and T-cell priming. Consequently, the molecular mechanisms underlying DC dysfunction in tumors remain a critical barrier to improving cancer immunotherapy. Our ongoing research is focused on developing next-generation DC-directed immunotherapies that elicit durable and effective anti-tumor immune responses.

3. Reprogramming the Tumor Microenvironment to Restore Anti-tumor Immunity: A major barrier to durable therapeutic responses to cancer is the establishment of an immunosuppressive tumor microenvironment (TME), which promotes tumor progression while limiting effective anti-tumor immunity. The TME is composed of malignant cells, stromal cells, endothelial cells, and diverse immune populations that engage in dynamic interactions through cytokines, chemokines, metabolites, and immune checkpoint pathways. These interactions drive the accumulation of dysfunctional dendritic cells, tumor-associated macrophages, myeloid-derived suppressor cells, regulatory T cells, and exhausted T cells, collectively suppressing cytotoxic immune responses and fostering resistance to immunotherapy. Although immune checkpoint blockade has transformed cancer treatment, most patients with solid tumors fail to achieve durable clinical benefit, underscoring the need to better understand the mechanisms that establish and maintain an immunosuppressive TME. The long-term goal of our research is to develop mechanism-based immunotherapies that convert immunologically “cold” tumors into T cell-inflamed, therapy-responsive tumors. Our research objective is to define the molecular and cellular mechanisms that regulate immune suppression within the TME and determine how therapeutic targeting of these pathways restores anti-tumor immunity.

We currently looking for highly motivated students and postdoctoral fellows. 

2015  BD Immunology Award

2014  New Innovator Award, Leukemia Research Foundation, USA

2007  Best Ph.D thesis work award, University of Tubingen, Germany

2005  ASH Travel Award, American Society  of Hematology, USA

2000  Best Research Presentation Award, SASTRA University, India

Active Grants:

Grant 1:

Source = NIH/ NIAID

Budget = $3, 677, 656

Period = 2024 - 2029

Role = Principal Investigator

Grant 2 (PENDING):

Source = NIH/ NHLBI

Budget = $ 1, 943, 750

Period =  2026 – 2031

Role = Principal Investigator

Completed Grants: 

2023 – 2025 AI174952  (Role: Principal Investigator)

                           Decoding HIV-1 mediated Hematopathology

                           National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIAID)

2017-2022   R01HL132194  (Role: Principal Investigator)

                          NF-kB signaling in the control of Hematopoiesis

                          National Institutes of Health/National Heart Lung Blood Institute  (NHLBI)

2014-2015  Role: Principal Investigator

                        Role of A20 in the restriction of myeloid Leukemia

                        Leukemia Research Foundation

2010-2011  Role: Lead Investigator

                       Genetic & Molecular Control of E3 Ubiquitin Ligases in Stem Differentiation

                       National Institues of Health (NCRR),  5P20RR018757-09