Major Areas of Research
- Diagnosis, natural history and treatment of autoimmune lymphoproliferative syndrome (ALPS) and related disorders of immune-dysregulation leading to cytopenias and lymphoproliferation.
Dr. Rao’s current research and clinical activities focus on autoimmune lymphoproliferative syndrome (ALPS) and the related RAS-associated leukoproliferative disorder (RALD). ALPS is due to defect in the FAS gene leading to unusually high numbers of lymphocytes that accumulate in the lymph nodes, liver, and spleen, which can lead to enlargement of these organs.
Paradigms learnt from diagnosing and managing ALPS are applicable to other similar inherited immune disorders. For example, defects in PI3Kinase, CTLA4, LRBA, MagT1, and STAT3 can also lead to nonmalignant lymphoproliferation and autoimmune/autoinflammatory complications due to an aberrant lymphocyte life cycle. Affected lymphocytes infiltrate the bone marrow, lungs, liver, kidneys, and brain leading to complex symptoms that can require multidisciplinary clinical care teams and long-term follow up and research. These diseases affect both children and adults and have a predilection to hypersplenism and lymphomas, as well as autoimmune complications leading to low blood cell counts (cytopenias) and other end organ damage.
Many of these novel genetic defects are often being identified in patients presenting with cytopenias and lymphoproliferation mimicking ALPS and referred to the NIH Clinical Center for further evaluation. Hence Dr. Rao, along with a team of astute clinician collaborators,are interested in studying patients and families with cytopenias, nonmalignant lymphoproliferation, immunodeficiency, and as yet undetermined genetic defects.
Dr. Rao received his undergraduate and pediatric post-graduate medical education at SCB Medical College (Cuttack, Odisha, India) followed by Hematology training at the CMC Hospital (Vellore, India) and the Tata Memorial Hospital (Mumbai, India). Dr. Rao then undertook specialized training through a Hematology fellowship in Australia at Westmead and Sydney Children’s Hospital, followed by a pediatric hematology oncology fellowship at the National Cancer Institute in Bethesda, Maryland in 1995. Dr. Rao qualified as a Fellow of the Royal College of Pathologists of Australasia (FRCPA). Since 2003, Dr. Rao has been a staff physician in NIAID conducting clinical research and providing care for patients with ALPS and related disorders. Since 2006, Dr. Rao has chaired the NIAID Institutional Review Board (IRB) overseeing clinical research protocols.
Rao VK, Webster S, Dalm VASH, Šedivá A, van Hagen PM, Holland S, Rosenzweig SD, Christ AD, Sloth B, Cabnski M, Joshi AD, de Buck S, Doucet J, Guerini D, Kalis C, Pylvaenaeinen I, Soldermann N, Kashyap A, Uzel G, Lenardo MJ, Patel DD, Lucas CL, Burkhart C. Effective 'Activated PI3Kδ Syndrome'-targeted therapy with the PI3Kδ inhibitor leniolisib. Blood. 2017 Nov 23;130(21):2307-2316. doi: 10.1182/blood-2017-08-801191.
Rao VK. Approaches to Managing Autoimmune Cytopenias in Novel Immunological Disorders with Genetic Underpinnings Like Autoimmune Lymphoproliferative Syndrome. Front Pediatr. 2015 Jul 21;3:65. doi: 10.3389/fped.2015.00065. eCollection 2015.
Calvo KR, Price S, Braylan RC, Oliveira JB, Lenardo M, Fleisher TA, Rao VK. JMML and RALD (RAS-associated autoimmune leukoproliferative disorder): common genetic etiology yet clinically distinct entities. Blood. 2015 Apr 30; 125(18): 2753-8.
Price S, Shaw PA, Seitz A, Joshi G, Davis J, Niemela JE, Perkins K, Hornung RL, Folio L, Rosenberg PS, Puck JM, Hsu AP, Lo B, Pittaluga S, Jaffe ES, Fleisher TA, Rao VK, Lenardo MJ.Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations. Blood. 2014 Mar 27;123(13):1989-99.
Rao VK, Oliveira JB. How I treat autoimmune lymphoproliferative syndrome. Blood. 2011 Nov 24;118(22):5741-51. Updated 2015.
Oliveira JB, Bleesing JJ, Dianzani U, Fleisher TA, Jaffe ES, Lenardo MJ, Rieux-Laucat F, Siegel RM, Su HC, Teachey DT, Rao VK. Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome: report from the 2009 NIH International Workshop. Blood. 2010 Oct 7;116(14):e35-40.
Current Clinical Protocols
- Study of the Immunopathogenesis, Natural History, and Genetics of Autoimmune Lymphoproliferative Syndrome (ALPS) Associated with an Expansion of CD4-8-/TCR alpha/beta+ T Cells and Defective Lymphocyte Apoptosis (93-I-0063).
- Novel Genetic Disorders of the Immune System (14-I-0206).
- An open-label, non-randomized, within-patient dose-finding study followed by a randomized, double-blind placebo-controlled study with extension to assess the safety and efficacy of CDZ173 in patients with APDS/PASLI (15-I-0135).
- Extended treatment of CDZ173 under single patient IND in a patient with APDS/PASLI (Activated phosphoinositide 3-kinase delta syndrome/p110δ-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency) (16-I-0067).