The major focus of research in the Ross laboratory is to identify novel mechanisms of kidney injury occurring in HIV-positive persons and his laboratory uses in vitro and murine models to generate new strategies to prevent and treat kidney diseases. Dr. Ross also works with members of the International Network for Strategic Initiatives in Global HIV Treatment (INSIGHT) to perform research on kidney disease in the context of large international HIV treatment trials.

Ongoing NIH-funded projects:

Mechanisms by which antiretroviral medications protect kidneys from HIV-induced injury:

Though combination antiretroviral therapy (cART) is efficacious in preventing and treating HIV-associated nephropathy (HIVAN), the mechanisms by which these medications protect the kidney from the deleterious effects of HIV are poorly understood.  We are performing studies using transgenic animal models and molecular and genomic techniques to identify novel pathways by which ART protect the kidneys from HIV.  Moreover, we have exciting data suggesting that these medications may protect kidneys from non-viral mediated forms of kidney injury, including diabetic kidney disease.

The role of APOL1 polymorphisms in promoting HIV-induced kidney injury:

Polymorphisms in the APOL1 gene account for most of the excess risk of African-Americans to non-diabetic kidney disease and HIV-associated kidney disease in particular. In our studies, we are using genetically modified human kidney cells to perform innovative proteomic, and genomic studies to identify novel mechanisms by APOL1 genetic variants predispose to HIV-induced kidney injury. 

Most relevant publicatiion in past 10 years:

*Mocroft, A., Wyatt, C., Szczech, L., Neuhaus, J., El-Sadr, W., Tracy, R., Kuller, L., Shlipak, M., Angus, B., Klinker, H., and Ross, MJ. Interruption of antiretroviral therapy is associated with increased plasma cystatin C: Results from the SMART Study. AIDS. 23, 71-82. 2009.

*Snyder A, Alsauskas Z, Gong P, Rosenstiel P, Klotman M, Klotman P, Ross MJ: FAT10: a novel mediator of Vpr-induced apoptosis in HIV-associated nephropathy. J Virol. 83;11983-11988. 2009.

*Gong, P., Canaan, A., Wang, B., Leventhal, S., Snyder, A., Nair, V., Cohen, C. D., Kretzler, M., D'Agati, V., Weissman, S., and Ross, M. J. The ubiquitin-like protein FAT10 mediates NF-kappaB activation. J Am Soc Nephrol. 21:316. 2009.

Snyder A, Alsauskas ZC, Leventhal JS, Rosenstiel PE, Gong P, Chan J, Barley K, He C, Klotman M, Ross MJ, Klotman PE. HIV-1 viral protein r induces ERK and caspase-8 dependent apoptosis in renal tubular epithelial cells. AIDS, 24:1107-1119. 2010.

Neuhaus, J., Jacobs, D.R., Baker, J.V., Calmy, A., Duprez, D., La Rosa, A., Kuller, L., Pett, S.L., Ristola, M., Ross, M.J., Shlipak, M., Tracy, R., and Neaton, J.D. Markers of Inflammation, Coagulation and Renal Function Are Elevated in Adults with HIV Infection. J Infect Dis. 201:1788-1795. 2010.

Chen, P., Chen, B.K., Mosoian, A., Hays, T., Ross, M.J., Klotman, P.E., and Klotman, M.E. Virological Synapses Allow HIV-1 Uptake and Gene Expression in Renal Tubular Epithelial Cells. J Am Soc Nephrol.  22(3): 496-507. 2011.

Leventhal, J.S., Alsauskas, Z., Snyder, A., Gong, P., Wang, B., D’Agati, V., and Ross, M.J. Renal HIV Expression Is Unaffected by Serum LPS Levels in an HIV Transgenic Mouse Model of LPS Induced Kidney Injury. PLoS One. 6:e20688. 2011.

Papeta, N., Kiryluk, K., Patel, A., Sterken, R., Kacak, N., Snyder, H.J., Imus, P.H., Mhatre, A.N., Lawani, A.K., Julian, B.A., Wyatt, R.J., Novak, J., Wyatt, C.M., Ross, M.J., Winston, J.A., Klotman, M.E., Cohen, D.J., Appel, G.B., D’Agati, V.D., Klotman, P.E., and Gharavi, A.G. APOL1 variants increase risk for FSGS and HIVAN but not IgA nephropathy. J Am Soc Nephrol. 22:1991-1996. 2011.

Mocroft A, Neuhaus J, Peters L, Ryom L, Bickel M, Grint D, Koirala J, Szymczak A, Lundgren J, Ross MJ*, Wyatt CM*: Hepatitis B and C Co-Infection Are Independent Predictors of Progressive Kidney Disease in HIV-Positive, Antiretroviral-Treated Adults. PLoS ONE 7:e40245, (*co-senior authors). 2012.

Ryom L, Mocroft A, Kirk O, Worm SW, Kamara DA, Reiss P, Ross M, Fux CA, Morlat P, Moranne O, Smith C, Lundgren JD: Exposure to Antiretrovirals (ARVs) and Risk of Renal Impairment among HIV-positive Persons with Normal Baseline Renal Function: the D:A:D study. J Infect Dis 2013.

Ganesan A, Krantz EM, Huppler Hullsiek K, Riddle MS, Weintrob AC, Lalani T, Okulicz JF, Landrum M, Agan B, Whitman TJ, Ross MJ, Crum-Cianflone NF: Determinants of incident chronic kidney disease and progression in a cohort of HIV-infected persons with unrestricted access to health care. HIV Med 14:65-76, 2013

Ryom L, Mocroft A, Kirk O, Worm SW, Kamara DA, Reiss P, Ross M, Fux CA, Morlat P, Moranne O, Smith C, Lundgren JD; D:A:D Study Group. Association between antiretroviral exposure and renal impairment among HIV-positive persons with normal baseline renal function: the D:A:D study. J Infect Dis. 1;207(9):1359-69. 2013.

Lucas, G., Cozzi-Lepri, A., Wyatt, C., Post, F., Bormann, A., Crum-Cianflone, N., and Ross, M. Glomerular filtration rate estimated using creatinine, cystatin C or both markers and the risk of clinical events in HIV-infected individuals. HIV Med 15:116-123. PubMed PMID: 24024499. 2014.

Lucas, GM, Ross, MJ, Stock, PG, Shlipak, MG, Wyatt, CM, Gupta, SK, Atta, MG, Wools-Kaloustian, KK, Pham, PA, Bruggeman, LA, Lennox, JL, Ray, PE, and Kalayjian, RC. Clinical Practice Guideline for the Management of Chronic Kidney Disease in Patients Infected With HIV: 2014 Update By the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis; 59(9), e96-e138. 2014.

Ryom, L., Mocroft, A., Kirk, O., Ross, M., Reiss, P., Fux, C. A., Morlat, P., Moranne, O., Smith, C., El-Sadr, W., Law, M., and Lundgren, J. D. Predictors of advanced chronic kidney disease and end-stage renal disease in HIV-positive persons. AIDS 28, 187-199. 2014.

Mocroft A, Lundgren J, Ross M, Law M, Reiss P, Kirk O, Smith C, Wentworth D, Heuhaus J, Fux C, Moranne O, Morlat P, Johnson M, Ryom L; Data on Adverse Events  (D:A:D) study group, the Royal Free Hospital Clinic Cohort and the INSIGHT study  group. A clinically useful risk-score for chronic kidney disease in HIV infection. J Int AIDS Soc ;17(4 Suppl 3):19514.. PMID: 25394023; PMCID: PMC4224906. 2014.

Leventhal, J.S., He, J.C., and Ross, M.J. Autophagy and Immune Response in Kidneys. Semin Nephrol. 34(1):53-61. 2014.

Ross, M. J. (2014). Advances in the pathogenesis of HIV-associated kidney diseases. Kidney Int. 86, 266-274. 2014.

Mocroft A, Lundgren JD, Ross M, Law M, Reiss P, Kirk O, Smith C, Wentworth D, Neuhaus J, Fux CA, Moranne O, Morlat P, Johnson MA, Ryom L; D:A:D study group; Royal Free Hospital Clinic Cohort; INSIGHT study group; SMART study group; ESPRIT study group. Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D study. PLoS Med. 2015 Mar 31;12(3):e1001809. PMID: 25826420; PMCID: PMC4380415. 2015.

Wolf T, Ross MJ*, and Davenport A. Minimizing risks associated with renal replacement therapy in patients with Ebola Virus Disease. Kidney Int. 2015. 87, 5-7. 2015.

Achhra AC, Mocroft A, Ross MJ, Ryom L, Lucas GM, Furrer H, Neuhaus J, Somboonwit C, Kelly M, Gatell JM, Wyatt CM; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) START Study Group. Kidney disease in antiretroviral-naïve HIV-positive adults with high CD4 counts: prevalence and predictors of kidney disease at enrolment in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial. HIV Med;16 Suppl 1:55-63. PMID: 25711324; PMCID: PMC4341947. 2015.

Mocroft A, Lundgren JD, Ross M, Fux CA, Reiss P, Moranne O, Morlat P, Monforte Ad, Kirk O, Ryom L; Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) Study. Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study. Lancet HIV. 3:e23-32. 2016.

Leventhal JS, Ni J, Osmond M, Lee K, Gusella GL, Salem F, Ross MJ. Autophagy Limits Endotoxemic Acute Kidney Injury and Alters Renal Tubular Epithelial Cell Cytokine Expression. PLoS One. 11(3):e0150001. 2016.

Ryom, L, Lundgren, JD, Ross, M, Kirk, O, Law, M, Morlat, P, Smit, C, Fontas, E, Fux, CA, Hatleberg, CI, de Wit, S, Sabin, CA, Mocroft, A, D:A:D, SG. Renal Impairment and Cardiovascular Disease in HIV-positive Individuals; The D:A:D Study. J Infect Dis. PMID: 27485357. 2016.

Ryom L, Mocroft A, Kirk O, Reiss P, Ross M, Smith C, Moranne O, Morlat P, Fux CA, Sabin C, Phillips A, Law M, Lundgren JD; D:A:D study group.. Predictors of eGFR progression, stabilisation or improvement after chronic renal impairment in HIV-positive individuals. AIDS. 2017 Mar 28. PMID: 28353536.

Nadkarni GN, Wyatt CM, Murphy B, Ross MJ. APOL1: a case in point for replacing race with genetics. Kidney Int. 2017 Apr;91(4):768-770. PMID: 28314574.

Rednor SJ, Ross MJ. Molecular Mechanisms of Injury in HIV-Associated Nephropathy. Front Med (Lausanne). 2018; 5:177. PMID: 29930940 PMCID: PMC5999756

Ross MJ, Coates PT. Using CRISPR to inactivate endogenous retroviruses in pigs: an important step toward safe xenotransplantation. Kidney Int. 2018; 93:4-6, PMID: 29198467.

Ross MJ. New Insights into APOL1 and Kidney Disease in African Children and Brazilians Living With End-Stage Kidney Disease. Kidney Int Rep. 2019; 4:908-910 PMC6611947.

Ryom L, Dilling Lundgren J, Reiss P, Kirk O, Law M, Ross M, Morlat P, Andreas Fux C, Fontas E, De Wit S, D'Arminio Monforte A, El-Sadr W, Phillips A, Ingrid Hatleberg C, Sabin C, Mocroft A. Use of Contemporary Protease Inhibitors and Risk of Incident Chronic Kidney Disease in Persons With Human Immunodeficiency Virus: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study. J Infect Dis. 2019 Oct 8;220(10):1629-1634. doi: 10.1093/infdis/jiz369. PubMed PMID: 31504669; PubMed Central PMCID: PMC6782100.

Gao X, Rosales A, Karttunen H, Bommana GM, Tandoh B, Yi Z, Habib Z, Agati V, Zhang W, Ross MJ. The HIV protease inhibitor darunavir prevents kidney injury via HIV-independent mechanisms. Sci Rep. 2019 Nov 1;9(1):15857. doi: 10.1038/s41598-019-52278-3. PubMed PMID: 31676833; PubMed Central PMCID: PMC6825220.

Townsend RR, Guarnieri P, Argyropoulos C, Blady S, Boustany-Kari CM, Devalaraja-Narashimha K, Morton L, Mottl AK, Patel U, Palmer M, Ross MJ, Sarov-Blat L, Steinbugler K, Susztak K. Rationale and design of the Transformative Research in Diabetic Nephropathy (TRIDENT) Study. Kidney Int. 2020 Jan;97(1):10-13. doi: 10.1016/j.kint.2019.09.020. PubMed PMID: 31901339.