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Chozha V. Rathinam, Dr. rer. nat.

Academic Title:

Associate Professor

Primary Appointment:


Additional Title:

Head, Laboratory of Stem Cell & Cancer Biology, The Institute of Human Virology


725 West Lombard Street, Baltimore, MD 21201

Phone (Primary):


Phone (Secondary):


Education and Training

Dr. Chozha Rathinam completed his doctoral (Dr. rer. nat./ Ph.D.) studies at the prestigious Hannover Medical School, Germany under the  supervision of Dr. Christoph Klein.    

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.

For more than a decade, research in Dr. Rathinam’s laboratory has been focusing  on major intrinsic and extrinsic molecular circuits that cause stem cell-based pathology and inflammatory disorders, immunodeficiencies and aging.  

Research/Clinical Keywords

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

Highlighted Publications

1. Silvestri G and Rathinam CV. Trim28 plays an indispensable role in maintaining functions and transcriptional integrity of hematopoietic stem cells.  bioRxiv.

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).


Additional Publication Citations

16.  Benedetti F, Mongodin EF, Badger JH, Munawwar A, Cellini A, Yuan W, Silvestri G, Kraus CN, Marini S, Rathinam CV, Salemi M, Tettelin H, Gallo RC, Zella D. Bacterial DnaK reduces the activity of anti-cancer drugs cisplatin and 5FU. Journal of Translational Medicine  22, 269 (2024). 
17. Benedetti F, Silvestri G, Denaro F, Finesso G, Contreras-Galindo R, Munawwar A, Williams S, Davis H, Bryant J, Wang Y, Radaelli E, Rathinam CV, Gallo RC, Zella D.  Mycoplasma DnaK expression increases cancer development in vivo upon DNA damage. Proc Natl Acad Sci USA 121, 10 (2024).
18. Benedetti F, Silvestri G, Denaro F, Finesso G, Contreras-Galindo R, Munawwar A, Williams S, Davis H, Bryant J, Wang Y, Radaelli E, Rathinam CV, Gallo RC, Zella D.  Mycoplasma DnaK increases DNA copy number variants in vivo. Proc Natl Acad Sci USA. 120, 30 (2023).
19. Sahai A, Jones DL, Hughes M, Pu A, Williams K, Iyer SR, Rathinam CV, Davis DL, Lovering RM, Gilotra MN.
Fibroadipogenic progenitor cell response peaks prior to progressive fatty infiltration after rotator cuff tendon tear. Journal of Orthopaedic Research. (2022).
20. Kode A, Mosialou I, Manavalan SJ, Rathinam CV, Friedman RA, Teruya-Feldstein J, Bhagat G, Berman E, Kousteni S. FoxO1-dependent induction of acute myeloid leukemia by osteoblasts in mice. Leukemia 30,1-13 (2016).

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. CD45RBlo 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).

Research Interests

For more than a decade research at the Rathinam laboratory (@ Columbia University and University of Maryland) has contributed significantly towards an understanding on the fine-tuning of inflammatory circuits, mediated by key regulators of the NFKB pathway- A20 and IKK2, in hematopoietic defects and immune dysfunctions. While these studies have unequivocally demonstrated the pathological effects of uncontrolled infection and inflammation in animal models, the consequences of chronic viral infections on human hematopoiesis remain unclear. In particular, the physiological consequences of human immunodeficiency virus (HIV)-1 induced chronic inflammation on human hematopoietic stem cells need to be identified.  The current research of the Rathinam lab aims to unravel the cellular mechanisms through which HIV-1 affects hematopoiesis and contributes to pathophysiology in humans. 

The major lines of our current investigation include:

1. Decoding inflammatory circuits that drive immune dysfunctions in HIV- exposed, but uninfected, infants born to HIV-infected mothers: An estimated 1.3 million HIV-exposed, uninfected (HEU) children are born annually to mothers-living with HIV. A vast majority of HEU children have higher risk for opportunistic infections within the first 6 months of life, most likely due to hematopoietic & immune defects. Even though a great deal of information is available on HIV-induced hematopoietic defects in people living with HIV, hematopathologies caused by in-utero exposure of HIV in HIV-exposed uninfected (HEU) children remains largely unknown. Particularly, physiological impact of maternal exposure of HIV on hematopoietic stem cells (HSCs) of HEU infants remain completely unknown. A vast majority of HEU children have higher risk of opportunistic infections within the first 6 months of life. Indeed, HEU infants have 2- to 4- fold higher mortality rate, largely due to respiratory infections and bacterial sepsis, when compared with HIV-unexposed uninfected (HU) infants. While the clinical relevance of respiratory tract infections is well recognized, defective immune circuitry that predisposes HEU infants/children to these infections remains unidentified. In addition, the upstream circuitry responsible for hematopoietic/immune defects in HEU infants/children remains unidentified. While HIV- associated hyperinflammation is recognized as the hallmark feature in HEU children, the pathophysiological impact of inflammation on HSC maintenance and functions remains elusive. Our current research is crafted to unravel the cellular and molecular players of inflammation that cause HSC defects in HEU infants/children. In addition, our studies are aimed to identify the role of specific immune subsets of HEU infants/children in providing immunity against respiratory tract infections. Finally, we would identify the cellular source of inflammation and evaluate the therapeutic benefits of inhibiting inflammatory circuits in HEU infants/children.  We believe that our research study would be of major clinical relevance as it attempts to unravel the cellular and molecular mechanisms that may be responsible for increased morbidities and mortalities in HEU children. A deeper understanding on HIV-induced pathophysiological consequences on HSCs may define potentially new targets for treating hematologic/immune disorders and identify novel targets that prevent HIV-induced immunodeficiencies.

2. Deciphering HIV-induced hematopathology: Hematological abnormalities, such as thrombocytopenia, anemia, lymphocytopenia, monocytopenia, and neutropenia, frequently occur in patients infected with Human Immunodeficiency Virus (HIV)-1. Of note, Pancytopenia has been considered as the hallmark feature of patients with advanced acquired immunodeficiency syndrome (AIDS) (Group IV). In addition, patients with HIV infection are susceptible to HIV-associated opportunistic infections and bone marrow neoplasms. More importantly, antiretroviral treatments result in incomplete rescue of hematopoiesis and are known to impair normal hematopoiesis in patients with HIV infection. Emerging evidence establish a strong link between HIV-1 and hematopoietic stem cells (HSCs) of the bone marrow. Overall, these studies provide a compelling rationale for further investigations into mechanisms through which HIV-1 dysregulates hematopoiesis. However, the cellular mechanisms responsible for pancytopenia and bone marrow failure following HIV-infection remain incompletely understood.  More importantly, it remains unclear if HIV infection is directly affecting the physiology and functions of HSCs. A deeper understanding of the cellular and molecular mechanisms that regulate HSCs in the BM of patients with HIV-1 infection would be valuable in designing novel therapies for HIV-associated hematological diseases. Therefore, our research aims to unravel the physiologic impact of HIV infection on HSCs and to identify the progenitors that are susceptible to HIV infection. We believe that the proposed research will provide detailed insights into the mechanisms through which HIV infection impairs HSC physiology and causes hematopathology. Knowledge obtained from these studies would be useful to design novel and more effective therapies for human hematologic diseases that are caused by pathogenic viruses, such HIV-1.

3. Unraveling the impact of HIV-induced chronic inflammation on innate immune system: Earlier studies have unequivocally established that dendritic cells (DCs) play pivotal roles in the control of human immunodeficiency virus (HIV)-1 infection at both acute and chronic phases. Untreated people living with HIV (PLWH) exhibit reduced frequencies of DCs in the peripheral blood. Interestingly, there exists an inverse correlation between depletion of circulating DCs and disease progression during HIV-1 infections. In agreement with these findings, DCs (particularly myeloid DCs) from elite controllers exhibit reduced spontaneous immune activation; increased functions in response to TLR activation; augmented abilities to recognize HIV-1; and increased capacities in inducing antiviral HIV-1-specific T cells, when compared to uninfected, untreated PLWH and Anti-retroviral therapy(ART)-treated PLWH. More importantly, recent studies establish that the current ART regimen does not restore DC deficiencies observed in PLWH. While thediminished numbers of DCs in the PBMCs of PLWH have been well documented, cellular, and molecular mechanisms responsible for this phenomenon remain largely unknown.  To this end, our current research is designed to unravel the physiologic impact of HIV infection on DC differentiation and to identify the mechanisms responsible for reduced DC differentiation in PLWH.  Understanding cellular and molecular mechanisms through which HIV-1-infection induces DC defects should help us in the fight against HIV-1 infection. Our studies will contribute to the design of novel treatment strategies preventing HIV-induced immune dysfunctions.

4. Understanding the Brain-bone marrow crosstalk during neural injuriesTraumatic brain injury (TBI) is one of the major causes of morbidity and disability worldwide.  Approximately, 1.7 million people are afflicted by TBI every year and contributes to 30 % of all injury related deaths.  The annual cost of treatment, within the United States, for patients with TBI is ~$60 billion. TBI involves a spectrum of pathoanatomical subtypes and induces complex pathophysiological pathways. In addition to causing severe trauma in the brain, TBI initiates a cascade of cellular, molecular, biochemical and immunological events that are referred to as “secondary injury”.  Indeed, clinical outcome of TBI is often determined by the nature and severity of both primary and secondary injuries. Neuroinflammation is an adverse outcome and a key manipulable aspect of secondary injury following TBI.  While the clinical significance of tightly controlled neuroinflammation has begun to unfold, the pathophysiological consequences of TBI mediated neuroinflammation remain incompletely understood. Inadequate knowledge on systemic defects caused by TBI is believed to be one of the major challenges in designing effective therapies. Recent research from our laboratory has discovered major immunodeficiencies caused by TBI-induced neuroinflammation.   We are currently identifying the cellular and molecular players that participate in and control the neuro-immune crosstalk. We believe that our studies would provide insights on novel therapeutic strategies towards treatment of patients suffering from TBI.

We currently looking for highly motivated students and postdoctoral fellows. 

Awards and Affiliations

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

Grants and Contracts

Active Grants:

Grant 1:

Source = NIH/ NIAID

Budget = $3, 677, 656

Period = May 2024 -April, 2029

Role = Principal Investigator


Grant 2:

Source = NIH/ NIAID

Budget = $ 424, 875

Period = Feb 2023 – Jan 2025

Role = Principal Investigator


Completed Grants: 

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