- Consulting Nephrologist, Mark Hatfield Clinical Research Center, NIH, Present
- Commissioned Officer (Captain), U.S. Public Health Service, Retired
- Adjunct Professor of Medicine, Uniformed Services University of the Health Sciences, Present
- Branch Chief, Kidney Diseases Branch, NIDDK, 2013 - present
- Senior Investigator, NIDDK, NIH, 1995-present
- Medical Staff Fellow, NIH, 1987-1995
- Complete Training in Internal Medicine and Nephrology, University of Washington, 1987
- M.D., University of Pennsylvania Medical School, 1980
- B.A., Harvard College, 1975
Dr. Kopp leads a translational research group within the Kidney Disease Section, Kidney Diseases Branch, studying focal segmental glomerulosclerosis (FSGS) and related podocyte diseases.
- Chromosome 22 harbors a major risk locus for kidney disease in African Americans, including FSGS, HIV-associated nephropathy, and arterionephrosclerosis (hypertension-attributed kidney disease). APOL1 coding variants, which protect against trypanosomal infection, are strongly associated with kidney disease (odds ratios 7-29). The mechanism of glomerular injury is unknown.
- The HIV-1 protein Vpr, expressed in the glomerular podocytes, is sufficient to reproduce the chief features of HIV-associated collapsing glomerulopathy in transgenic mice.
Current Research Efforts
- determining the mechanisms by which Apol1 variants damage the glomerulus
- examining whether cardiotrophin-like cytokine 1 is a permeability factor that contributes to recurrent FSGS following kidney transplant
- an open label phase II trial examining the efficacy of rituximab combined with cyclosporine (for 48 weeks) for treatment of refractory podocyte disease
- participating in the ORD-funded NEPTUNE study of nephrotic diseases
Information for Patients
- We are actively recruiting individuals with focal segmental glomerulosclerosis and those with undiagnosed nephrotic syndrome or proteinuria.
- All NIH trials are listed at clinicaltrials.gov.
- Information about glomerular diseases is available on the Glomerular Disease Primer page.
Reagents Available to the Research Community
- Podocin promoter/rTTA (reverse tetracycline transactivator)—also available from JAX and as herozygotes or homozygotes
- TRE (tet responsive element)/Vpr
- Alb/TGF-beta mice (request permission from Dr. Snorri Thorgeirsson, NCI)
- rabbit polyclonal antibody to Vpr1-50 peptide—also available from AIDS Research and Reference Reagent Program
- rabbit antiserum to human podocin (cross-reactive with mouse podocin)
- rabbit antiserum to human nephrin (no cross-reactivity with mouse nephrin)
- goat antimouse mesangial cell serum, for induction of glomerulonephritis in mice
Podocyte Cell Lines
- mouse podocytes, immortalized with thermosensitive SV40 T Ag and bearing podocin/rtTA, for expression of genes of interest in cultured mouse podocytes
- same, plus TRE silencer to reduce background expression
- human urine derived podocyte-like epithelial cells (HUPECs), immortalized with hTERT and thermosensitive SV40 T Ag
Please contact us for further details. NIDDK MTAs are available through Technology Advancement and Transfer.
- Survival Advantage of African American Dialysis Patients with End-Stage Renal Disease Causes Related to APOL1.
- Lertdumrongluk P, Streja E, Rhee CM, Moradi H, Chang Y, Reddy U, Tantisattamo E, Kalantar-Zadeh K, Kopp JB.
- Cardiorenal Med (2019) 9:212-221. Abstract/Full Text
- One Actor, Many Roles: Histopathologies Associated With APOL1 Genetic Variants.
- Kopp JB, Rosenberg AZ.
- Adv Anat Pathol (2019 May) 26:215-219. Abstract/Full Text
Research in Plain Language
Our lab wants to translate the results from research on kidney diseases into medical practices for people who have these diseases. We are studying causes and medical treatments for kidney diseases in which scarring occurs on parts of some of the glomeruli, the tissue structures in the kidney that filter unneeded and harmful substances out of the blood and into the urine. This disease condition is called focal segmental glomerulosclerosis (FSGS). Some highlights of what we have recently learned about FSGS include the following.
- APOL1 is a gene that encodes a protein tha contributes to normal kidney function. A particular variant of this gene accounts for much of the increased risk that individuals of African descent have for both FSGS and for a similar disorder that is associated with HIV infection. Individuals with this risk gene variant are five times more likely to develop FSGS than individuals with other normally occurring variants of the gene. They are seven times more likely (if HIV infected) to develop glomerular disease. Podocytes are the cells on the outside of the glomerulus that regulate what substances in the blood are filtered out into the urine and what substances are retained in the bloodstream. We are testing the hypothesis that this risk gene variant makes the podocytes more fragile. We are also trying to determine whether the scarring of the glomerulus (glomerulosclerosis) leads to high blood pressure or whether an existing tendency to have high blood pressure (essential hypertension) makes the fragile podocytes more susceptible to damage.
- We are investigating whether the risk gene variant affects how well kidney transplants function and whether kidney donors with the risk gene variant are more susceptible to glomerulosclerosis or to other signs of filtering problems, such as high levels of protein in the urine, after they donate.
- We are studying people with HIV to determine how many have signs of glomerular filtering problems, what changes in the glomerular tissue are correlated with these problems, and whether the risk gene variant is a factor in how their kidneys function over time.
- We are conducting clinical trials and working with other researchers to test medications or combinations of medications in treating diseases of podocytes or, more generally, disorders of the glomeruli.
- We also offer other researchers some of the specialized tools we have developed for conducting our research. These tools include mice with specific alterations in their genes (transgenic mice), biomolecules produced by the immune system that bind very specifically to certain substances or cell parts (antibodies), and cultures of podocytes with specific inherited properties (podocyte cell lines).