Subramaniam Malarkannan, PhD
- Professor, Departments of Medicine (Hematology & Oncology); Microbiology and Immunology; Pediatrics and CTSI
- Senior Investigator and Gardetto Chair for Immunology and Immunotherapy, Blood Research Institute, Blood Center of Wisconsin
Education and Awards
- 1992, Madurai Kamaraj University, PhD
- 2000, University of California-Berkeley,
- 1992, University of Geneva,
- 2011-Present Review Editor, Frontiers in NK cell Biology, Lausanne, Switzerland
- 2011-Present Editor, ISRN Immunology, New York, USA
- 2013-Present Guest Editor, Medical Sciences, Basel, Switzerland –“Recent advances in Cellular Immunotherapy”
- 2013-Present Associate Editor, Autoimmunity, Irvine, CA, USA
- 2013-Present Editor, Medical Sciences, Basel, Switzerland
- 2014-Present Review Editor, Frontiers in Tumor Immunology, Lausanne, Switzerland
National elected/appointed leadership and committee positions
- 2016 Chair, NIAID, ZRG IMM-F-02 Study Section, NIH
- 2016 Adhoc Reviewer, LCMI, NIH
- 2016 Adhoc Reviewer, NIAID, Innate Immunity and Inflammation (III) Study Section, NIH
- 2016 Reviewer, NIGM, R35 Review Panel
- 2017 Adhoc Reviewer, NIAID, Innate Immunity and Inflammation (III) Study Section, NIH
- 2017 Adhoc Reviewer, NIAID, ZRG-IMM-F-02, NIH
- 2017 Adhoc Reviewer, NIAID, ZRG-F07-U-20, NIH
- 2017 Adhoc Reviewer, NIAID, ZRG-IMM-U-81, NIH
International elected/appointed leadership and committee positions
- 2004 External Member, Grant Review Committee, Italian Society for Cancer Research, Italy
- 2009 External Member, Grant Review Committee, Agency for Science, Technology and Research (A*STAR), Biomedical Research Council of the Government of Singapore (BMRC)
- 2010 External Member, Grant Review Committee, Infection and Immunity Board, UK Medical Research Council (MRC), Extramural Program, UK.
- 2013 External Grant Reviewer, Swiss Cancer League, Bern, Switzerland
- 2014 External Grant Reviewer, National Science Centre, Poland.
- 2017 External Grant Reviewer, National Research Foundation (NRF), Government of Singapore.
Research and publications
Laboratory of Molecular Immunology and Immunotherapy
Blood Research Institute, Blood Center of Wisconsin
Our laboratory studies the basic biology and clinical utilization of natural killer (NK) cells. NK cells are a unique white blood cell that accounts for approximately 5-10% of circulating lymphocytes. While T cells need specific antigens to activate function, many malignant cells find ways to evade T-cell mediated death through down-regulation of these antigens. NK cells are naturally designed to target and kill malignant or dysregulated cells through a complex system of recognizing these cells. The following are the major areas of our focus:
Basic Biology of NK Cell Immunotherapy
The main focus of our laboratory is to evaluate the elaborate signaling mechanisms that drive how NK cells work. Hundreds of signaling molecules take part in transducing membrane-proximal events into meaningful cellular functions. Through a multitude of murine knock-out models, we can specifically test the role of each protein in this context. By investigating these pathways, our group has expanded knowledge of NK cell basic immunobiology.
Clinical and Translational Work in NK Cell-Mediated Immunotherapy
NK cells hold significant promise in the formulations of novel cellular immunotherapies targeted to chemo-resistant/relapsing malignant hematopoietic and solid tumors. Recent scientific breakthroughs have helped to formulate successful Chimeric Antigen Receptor (CAR)-based cellular immunotherapy, which is now FDA-approved for the treatment of B-cell precursor ALL that is refractory or in second or later relapse. However, CAR-mediated therapy can also cause a significant side effect called, 'cytokine-release syndrome' (CRS), a potentially fatal condition in two-thirds of patients due to uncontrolled inflammation. Formulations of novel methods that regulate inflammation are of high clinical relevance and are central to prevent CRS and improve the safety of CAR therapy.
Our current work focuses on generating NK cell-based novel immunotherapies. Our clinical group headed by Dr. Monica Thakar currently offers an un-manipulated NK cell-based immunotherapy to cancer patients. She employs a cellular and adoptive immunotherapy strategy that incorporates hematopoietic cell transplantation (HCT) followed by the infusion of donor-derived NK cells into cancer patients. Clinical grade NK cells are manufactured under FDA-approved IND BB 13794 (Dr. Thakar) and infused into the patients. This therapy is being offered at the Children’s Wisconsin and Froedtert Hospital. In addition, we are interested in defining the precise molecular mechanisms by which anti-tumor cytotoxicity and induction of inflammation are individually regulated in NK and T cells. This molecular blueprint is central to the success of the CAR-mediated clinical applications. Our group has identified a unique Fyn-ADAP-Carma1 signaling pathway that is exclusively responsible for the production of inflammatory cytokines, not anti-tumor cytotoxicity (61/866,348; 8/15/2013). We are currently working to engineer a ‘CRS-free-CAR’ therapy.