Vice Chair of Research
Mary Joy and Jerre Stead Professor of Pediatric Hematology/Oncology
Professor of Pediatrics
Primary Office: 1324 BT
200 Hawkins Drive
Iowa City, IA 52242
Lab: 3080 ML
Iowa City, IA 52242
MBBS, Gujarat University, Medicine
MBBS, Gujarat University, Surgery
MD, Gujarat University, Pediatrics
MBA, Executive-MBA Certification in Physician Leadership, Katz School of Business, University of Pittsburgh
Certificate, Leadership Development for Physicians in Academic Health Centers, Harvard T.H. Chan School of Public Health, Center for Executive and Continuing Professional Education
Residency, Gujarat University Civil Hospital, Pediatrics
Chief Resident, Gujarat University Civil Hospital, Pediatrics
Residency, New York University Medical Center, Pediatrics
Fellowship, Memorial Sloan-Kettering Cancer Center, Pediatric Hematology/Oncology
Fellowship, Memorial Sloan-Kettering Cancer Center, Special Clinical Fellow
Licensure and Certifications
Iowa Medical License, Iowa Board of Medicine
Board Certification, Pediatric Hematology-Oncology, American Board of Pediatrics
My laboratory research program focuses on explicating the molecular underpinnings of immune dysregulation and cancer development in children. The laboratory is consistently funded by the National Institutes of Health (NIH) through both R01 and R21 mechanisms. Two broad components of our research program are:
1. Wiskott-Aldrich Syndrome and immune dysregulation:
I have a longstanding interest in understanding the molecular underpinnings of the development of human immune responses in health and disease. We have chosen to use the genetic disease model of Wiskott-Aldrich syndrome (WAS) to determine the partners and pathways of WAS protein (WASp) participation in the regulation of CD4 T helper cell differentiation and the development of T cell adaptive immunity. Human WAS is an X-linked genetic disease manifesting in severe immune deficiency, autoimmunity, thrombocytopenia, and lymphoid cancers in young boys. In order to clarify WASp’s role in immune regulation in health, and immune dysregulation in WAS, our laboratory has taken the complementary approach of investigating the functions of WASp from both vantage points, i.e. cytoplasm and nucleus. Research from my laboratory was essential in revealing for the first time a novel nuclear function for WASp in the transcriptional regulation of Th1-differentiation through its effect on epigenetic modifications at the T-BET gene-promoter locus. Since that time, we have been actively involved in further understanding how WASp associates with and regulates protein pathways and gene networks that control development of protective type-1 immunity. We seek to explicate the molecular mechanism of WASp’s nuclear transport and its role on impacting Th1/Th2/Th17/Treg differentiation. We are particularly interested in understanding the molecular basis for the disease severity in WAS patients that carry single missense mutations that still allow the expression of mutant WASp. We are testing the hypothesis that the primary function of WASp is in coordinating the nuclear events of gene transcription that occur independently of its well-described cytoplasmic effect on the actin cytoskeleton. We believe our studies will have direct implications to the better design of therapeutics in WAS, a life-threatening childhood disease.
2. Investigating the Genome and Epigenome of Pediatric Acute Lymphoblastic Leukemia (ALL):
We have recently embarked on the studies of childhood ALL. Despite an improved understanding of the pathogenesis of childhood ALL from a cellular and molecular perspectives, the current knowledge of how the multiple genetic alterations (mutations, translocations, etc.) associated with ALL modify the disease severity and response to conventional chemotherapy is ill understood. It is also clear whether these genetic mutations are a cause (i.e., a driver event) or a consequence (i.e., a passenger event) for the development of ALL. Do these genetic/epigenetic events contribute directly to the primary treatment failures in childhood ALL is also unclear. Our research is aimed at understanding if and how the genomic and epigenomic landscapes of the leukemic blasts pattern the different severity grades of ALL. Whether such novel metric could be identified and ultimately used clinically to predict children who will respond to chemotherapy versus ones who will not.
Center, Program and Institute Affiliations
Holden Comprehensive Cancer Center
SUMOylation-disrupting WAS mutation converts WASp fro a transcriptional activator to a repressor of NF-kB response genes in T cells..
2015 August 10.
Distruption of hSWI/SNF-Complexes in T cells by WAS Mutations Distinguishes X-linked Thrombocytopenia from Wiskott-Aldrich Syndrome..
2014 November 27. 124(23):3409-19.
Congenital dyserythropoietic anemia type I presenting as persistent pulmonary hypertension and pigeon chest deformity.
Pediatr Blood Cancer.
2014 August. 61(8):1460-2.
Nuclear Role of WASp in Gene Transcription Is Uncoupled from its ARP2/3-Dependenct Cytoplasmic Role in Actin Polymerization..
2014 July 1. 193(1):150-60.
Mifamurtide in metastatic and recurrent osteosarcoma: A patient access study with pharmacokinetic, pharmacodynamic, and safety assessments..
Pediatr Blood Cancer.
2014 February. 61(2):238-44.
Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus mounted by CD4+ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis.
J Clin Invest.
2010 August 16. 120(9):3242-54.
Nuclear Role of WASp in the Pathogenesis of Dysregulated TH1-Immunity in Human Wiskott-Aldrich Syndrome.
SCIENCE Transl Med .
2010 June 23. 2(37):37-44.
Date Last Modified: 06/06/2016 -