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Immunity & Infectious Disease Lab

Nemours Biomedical Research

About the Immunity and Infectious Disease Lab

The Immunity and Infectious Disease Lab is concerned with a variety of conditions relating to immunology (the study of the immune system and associated disorders), rheumatology (the study and treatment of conditions affecting the joints and connective tissue), infectious diseases and inflammation.

The lab’s immunity and infectious disease research investigates the role that genetics and environment play in the pathogenesis (the origin and development) of autoimmune disease, immune dysregulation (an inappropriately strong or weak response by the immune system) in human immunodeficiency virus (HIV) infection, and identification of novel targets and innovative therapeutics for immune system disease.

Our approaches bridge molecular biology, biochemistry, model systems and translational research (turning lab-based discoveries into practical clinical applications).


Lab Staff & Equipment

 
Our Staff
Principal Investigator
Terri H. Finkel, MD, PhD

Chair, Department of Pediatrics, Pediatrician-in-Chief, Chief Scientific Officer, Nemours Children's Hospital
Terri H. Finkel, MD, PhD, is an internationally recognized leader in pediatric research. In 2011, 2012 and 2013, she was ranked by U.S. News & World Report as among the top 1 percent of pediatric rheumatologists in the nation, a distinction held by only 15 physicians. Dr. Finkel leads the integration of clinical, educational and research programs at Nemours Children’s Hospital in Lake Nona Medical City, Orlando.

Since 1990, Dr. Finkel has been a funded investigator of the National Institutes of Health (NIH), attracting and managing prominent multi-center research projects. Over the course of her career, she has received more than $10 million in grants. From 1999 to 2011, she was the Hollander Professor of Pediatric Rheumatology at University of Pennsylvania and Division Chief of Rheumatology at The Children’s Hospital of Philadelphia (CHOP). Dr. Finkel’s work has advanced our understanding of basic immunology, as well as in specific areas of autoimmune and infectious diseases.

Learn More About Dr. Finkel »


Current Research Group
  • Jiangfang Wang, Research Scientist
  • Zhengyu Ma, Research Scientist
  • Dawn Cook, Clinical Trials Manager
  • Raji Venkataraman, Research Assistant II
  • HuiHui Han, Research Fellow
 
Capabilities & Equipment

Our lab features the use of a Becton Dickinson FACSCanto II flow cytometer, a top-quality benchtop analyzer that helps count, characterize and analyze cells.

Safety precautions are taken in every immunity and infectious disease research procedure. The lab is a Biosafety-Level 2-rated lab. This means that lab personnel follow all biocontainment precautions required to isolate biological agents in an enclosed facility.

In addition to our own equipment, we have access to a number of high-end facilities at Sanford-Burnham Medical Research Institute, which brings leading-edge pediatric research projects and technology to Central Florida. Our lab is located within the Sanford-Burnham Medical Research Institute complex, across from Nemours Children’s Hospital in Lake Nona Medical City, Orlando.

Our access to Sanford-Burnham core facilities includes:
  • laboratory resources
  • cardiometabolic phenotyping (techniques to evaluate cardiovascular and metabolic functions in model systems)
  • cellular imaging (such as fluorescence microscopy, immunohistochemistry, high content screening and laser capture microdissection)
  • histology (the study of the microscopic anatomy of cells and tissues of plants and animals)
  • Nuclear magnetic resonance (NMR, the form of electromagnetic radiation used in magnetic resonance imaging, or MRI, scans)
  • protein production and analysis
  • analytical genomics (includes techniques such as DNA sequencing)
  • metabolomics (the scientific study of chemical processes that involve the products of metabolism)
  • bioinformatics (an interdisciplinary field that develops methods for storing, retrieving, organizing and analyzing biological data)
  • ultra-high throughput screening (a method used in drug discovery to quickly screen in excess of 100,000 compounds per day)
  • exploratory pharmacology (methods to assess the drug-like properties of compounds)
  • medicinal chemistry (provides general synthetic and medicinal chemistry resources)

Current Research

Terri H. Finkel, MD, PhD, and her team are using state-of-the-art genomic tools to study the latency (dormancy) of human immunodeficiency virus (HIV) and the potential impact of novel drug and gene therapy as a treatment for the disease. They are also working with an atomic force microscope to understand the behavior of T-cells (white blood cells that help the body fight diseases and harmful substances).

The lab is also continuing Dr. Finkel’s acclaimed immunity and infectious disease research on juvenile idiopathic arthritis (JIA) to identify genes that cause the debilitating disease and the environmental factors that trigger its onset. The goal is to create a road map for physicians to offer personalized medical therapies for children with JIA.

Specifically, these projects include:
 
Cell signaling in T-cell development and deployment

A key question in T-cell development is how T-cells are selected to live or die — a critical process in producing a healthy immune system able to fight infection without triggering autoimmunity (when the body initiates an immune response against its own cells and tissues).

Studying signal transduction (when a molecule outside the cell activates a cell’s signal receptor) in immature thymocytes (cells in the thymus that generate the T-cells), Dr. Finkel discovered that developing T-cells — previously thought to be unresponsive and inert (unmoving and doing little or nothing) — were able to receive and transmit cellular signals (Finkel TH, McDuffie M, Kappler JW, Marrack P, Cambier JC. Both immature and mature T cells mobilize Ca2+ in response to antigen receptor crosslinking. Nature. 1987;330:179-181. Finkel TH, Cambier JC, Kubo RT, et al.

The thymus has two functionally distinct populations of immature alpha beta + T cells: one population is deleted by ligation of alpha beta TCR. Cell. 1989;58:1047-1054).

Recent work has focused on mechanisms of triggering of the T-cell receptor for antigen (Ma Z, Sharp KA, Janmey PA, Finkel TH. Surface-anchored monomeric agonist pMHCs alone trigger TCR with high sensitivity. PLoS Biol. 2008;6:e43. Science Editors’ Choice 319: 1460, 2008. Ma Z, Finkel TH. Mechanical force in T cell receptor signal initiation. Frontiers in Immunol. 2012;3:217.), exploiting single molecule studies to determine how viruses escape from cytotoxic (toxic to cells) T-cell immune responses. Discovering this method of escape is a key step in developing vaccines for AIDS and other global infections.

 
Cell death in HIV pathogenesis and therapy

Dr. Finkel was the first to show that the HIV surface protein, gp120, primes T-cells for suicide (Banda NK, Bernier J, Kurahara DK, et al. Crosslinking CD4 by human immunodeficiency virus gp120 primes T cells for activation-induced apoptosis. Journal of Experimental Medicine. 1992;176:1099-1106).

In studies of in vivo (in living organisms) infection, her team showed that apoptosis (the normally occurring death of cells) occurs predominantly in bystander cells and only rarely in productively infected cells (Finkel TH, Tudor-Williams G, Banda NK, et al.

Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes. Nature Medicine. 1995;1:129-134), solidifying the concept of “bystander death” (death of nearby cells) in AIDS.

Ongoing studies (Wang J, Reuschel EL, Shackelford JM, et al. HIV-1 Vif promotes the G₁- to S-phase cell-cycle transition. Blood. 2011;227:1260-1269. PLoS Pathogens, in press) have identified novel cellular genes that regulate T cell apoptosis, cell cycle and possibly latency — the major hurdle to cure — in HIV infection.

They also include preclinical studies of a gene therapy targeting small interfering RNA (siRNA, molecules that interfere with the expression of specific genes) against one such gene to selectively kill HIV-infected cells.

 
Genes and environment in the pathogenesis of autoimmunity

Juvenile idiopathic arthritis (JIA) is a complex phenotype (an organism's observable characteristics or traits) that is likely determined by interactions between multiple genetic factors. In collaboration with more than 15 centers of pediatric rheumatology world-wide, Dr. Finkel conducted one of the first genome-wide studies of JIA and identified an association of the TRAF1-C5 genomic region with JIA (Behrens EM, Finkel TH, Bradfield JP, et al.

Association of the TRAF1-C5 locus on chromosome 9 with juvenile idiopathic arthritis. Arthritis Rheum. 2008;58:2206-2208). In collaboration with researchers at Cincinnati Children’s Hospital Medical Center, Dr. Finkel also identified an association of MUNC13-4 gene polymorphisms with macrophage activation syndrome, a life-threatening complication of systemic JIA (Zhang K, Birochak J, Passo MH, et al. Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis is associated with MUNC13-4 gene polymorphisms. Arthritis & Rheum. 2008;58:2892-2896).

In recent studies in more than 10,000 patients and controls, her team identified the chemokine (a signaling protein secreted by cells) receptor, CXCR4, as a novel, genome-wide, significant JIA risk factor. Work on this receptor could contribute significant protection from this crippling disease. The extensive literature surrounding the biology of CXCR4 in health and disease, and the availability of targeted therapeutic agents, make CXCR4 a particularly attractive candidate for drug development.

Contact the Immunity and Infectious Disease Lab

Jiangfang Wang

Research Scientist
(407) 745-2183
jiangfang.wang@nemours.org

Location

Immunity and Infectious Disease Lab Nemours Research
C/O Sanford-Burnham Medical Research Institute
6400 Sanger Road
Orlando, FL 32827


Clinical Trials

Browse our comprehensive list of clinical trials currently underway at Nemours facilities in Delaware and Florida.
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