Asha R Kallianpur, MD, MPH
Lerner Research Institute,
9500 Euclid Avenue, Cleveland, Ohio 44195
Dr. Kallianpur’s lab conducts translational research focused on understanding the roles played by iron transport and the genomic regulation of iron metabolism in chronic inflammatory conditions. Iron is essential for all metabolic and respiratory processes, but requires tight cellular compartmentalization due to its role in generating free radicals via Fenton chemistry. Both iron deficiency and iron excess also cause mitochondrial dysfunction, a factor implicated in chronic disease pathogenesis, but the role of iron in these diseases and their natural history is underappreciated and has not been well studied in humans. In addition, iron regulation has a major impact on innate immunity and the inflammatory response, which the Kallianpur lab studies in the setting of HIV infection.
Researchers in the Kallinapur lab exploit common iron-loading nuclear genetic variants, which in the heterozygous state are deemed "nonpathogenic," to study subclinically dysregulated iron metabolism and mitochondrial function in:
toxicities of high-dose chemotherapy
etiology and prognosis of estrogen-driven cancers
neurotoxicities of antiretroviral drugs used to treat HIV/AIDS worldwide.
As a clinician and population-based scientist, Dr. Kallianpur is interested in applying genetic epidemiologic methods to study the role of iron and the mitochondrial genome in a multitude of chronic, complex clinical phenotypes.
The Kallianpur lab examines the role that variation in iron metabolism and mitochondrial function (energy production) play in chronic inflammatory diseases and their complications. Of particular interest are HIV-associated neurocognitive disorders (HAND), which remain very common despite highly effective drugs that suppress the virus to undetectable levels. Their goal is to increase awareness of HAND in the HIV-infected population, promote screening for the disorder, and develop new ways to treat individuals at risk for HAND based on genomic factors.
- Hulgan T, Samuels DC, Bush W, Ellis RJ, Letendre SL, Heaton RK, Franklin DR, Straub P, Murdock DG, Clifford DB, Collier AC, Gelman BB, Marra CM, McArthur JC, McCutchan JA, Morgello S, Simpson DM, Grant I, Kallianpur AR; CHARTER Group. Mitochondrial DNA Haplogroups and Neurocognitive Impairment During HIV Infection.Clin Infect Dis. 2015 Jun 30.
- Kallianpur AR, Jia P, Ellis RJ, Zhao Z, Bloss C, Wen W, Marra CM, Hulgan T, Simpson DM, Morgello S, McArthur JC, Clifford DB, Collier AC, Gelman BB, McCutchan JA, Franklin D, Samuels DC, Rosario D, Holzinger E, Murdock DG, Letendre S, Grant I; CHARTER Study Group. Genetic variation in iron metabolism is associated with neuropathic pain and pain severity in HIV-infected patients on antiretroviral therapy. PLoS One. 2014 Aug 21;9(8):e103123.
- Kallianpur AR, Levine AJ. Host genetic factors predisposing to HIV-associated neurocognitive disorder. Curr HIV/AIDS Rep. 2014 Jul 5;11(3):336-352.
- Holzinger E, Hulgan T, Ellis R, Samuels DC, Ritchie MD, Haas DW, Kallianpur A, Bloss C, Clifford DB, Collier AC, Gelman BB, Marra CM, McArthur JC, McCutchan JA, Morgello S, Simpson DM, Franklin D, Rosario D, Selph D, Letendre S, and Grant I for the CHARTER Group. Full sequence mitochondrial DNA variation and HIV-associated sensory neuropathy in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort. Journal of Neurovirol. 2012;18(6):511-520.
- Crist M, Melekhin VV, Bian A, Shintani A, Milne G, Kallianpur A, Dageford LA, Haas DW, Hulgan T. Higher serum iron is associated with oxidant stress in HIV-infected men. J Acquir Immune Defic Syndr. 2013;64(4):367-73.
- Hulgan T, Haas DW, Haines JL, Ritchie MD, Robbins GK, Shafer RW, Clifford DB, Kallianpur AR, Summar M, Canter JA. Mitochondrial haplogroups and peripheral neuropathy during antiretroviral therapy: an adult AIDS clinical trials group study. AIDS. 2005;19(13):1341-9.
- Kallianpur AR, Hulgan T, Canter JA, Haines JL, Ritchie MD, Robbins GK, Shafer RW, Clifford DB, Haas DW. Hemochromatosis (HFE) gene mutations and peripheral neuropathy during antiretroviral therapy. AIDS. 2006;20(11):1503-13.
- Canter JA, Haas DW, Kallianpur AR, Ritchie MD, Robbins GK, Shafer RW, Clifford DB, Murdock DG, Hulgan T. The mitochondrial pharmacogenomics of haplogroup T: MTND2*LHON4917G and antiretroviral therapy-associated peripheral neuropathy. Pharmacogenomics J. 2008 Feb;8(1):71-7.
- Hulgan T, Tebas P, Canter JA, Mulligan K, Haas DW, Dubé M, Grinspoon S, Robbins GK, Motsinger AA, and Kallianpur AR; AIDS Clinical Trials Group 384 and A5005s Study Teams. Hemochromatosis (HFE) gene polymorphisms, mitochondrial haplogroups, and peripheral lipoatrophy during antiretroviral therapy: an AIDS Clinical Trials Group Study. J Infect Dis. 2008:197(6):858-66.
- Kallianpur AR, Hulgan T. The pharmacogenetics of nucleoside reverse-transcriptase inhibitor-associated peripheral neuropathy. Pharmacogenomics. 2009;10(4):629-637.
- Canter JA, Robbins G, Selph D, Clifford DB, Kallianpur AR, Shafer R, Levy S, Murdock D, Haas DW, Hulgan T and the ACTG Study 384 and NWCS 273 Study Teams. African Mitochondrial DNA subhaplogroups and peripheral neuropathy during antiretroviral therapy. J Infect Dis. 2010;201(11):1703-1707.
- Kallianpur AR, Jia P, Ellis RJ, Zhao Z, Bloss C, Wen W, Marra CM, Hulgan T, Simpson DM, Morgello S, McArthur JC, Clifford DB, Collier AC, Gelman BB, McCutchan JA, Franklin D, Samuels DC, Rosario D, Holzinger E, Murdock DG, Letendre SL, Grant I and the CHARTER Study Group. Genetic variation in iron metabolism is associated with neuropathic pain and pain severity in HIV-infected patients on antiretroviral therapy. PLoS One. 2014;9(8):e103123 Epub Aug 21.
- Canter JA, Kallianpur AR, Parl FF, Millikan RC. Mitochrondrial DNA G10398A polymorphism and invasive breast cancer in African-American women. Cancer Research. 2005;65(17):8028-33.
- Canter JA, Kallianpur AR, Parl FF, Millikan RC. Response to Mims et al regarding: “Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women”. Cancer Res. 2006; 66(3): 1880-1.
- Canter JA, Kallianpur AR, Fowke J. North American white mitochondrial haplogroups in prostate and renal cancer. J Urol. 2006 Nov;176(5):2308-9.
- Kallianpur AR, Hall LD, Yadav M, Christman BW, Dittus RS, Haines JL, Parl FF, Summar ML. Increased prevalence of the hemochromatosis (HFE) allele C282Y in women with breast cancer. Cancer Epidemiol Biomarkers Prev. 2004;13(2):205-12.
- Kallianpur AR, Hall LD, Yadav M, Byrne DW, Speroff T, Dittus RS, Haines JL, Christman BW, Summar ML. The hemochromatosis C282Y allele: a risk factor for hepatic veno-occlusive disease after hematopoietic stem cell transplantation. Bone Marrow Transplant. 2005;35(12):1155-64.
- Kallianpur AR, Lee SA, Gao YT, Lu W, Zheng Y, Ruan ZX, Dai Q, Shu XO, and Zheng W. Dietary animal-derived iron and fat intake and breast cancer risk in the Shanghai Breast Cancer Study. Breast Cancer Res Treat. 2008;107(1):123-32.
- Kallianpur AR, Lee SA, Xu WH, Zheng W, Gao YT, Cai H, Ruan ZX, Xiang YB, Shu XO. Dietary iron intake and risk of endometrial cancer: A population-based case-control study in Shanghai, China. Nutr Cancer. 2010;62(1):40-50.
- Kallianpur AR. Iron and Oxidative Injury—Commentary on "Fatty acid-mediated iron translocation: A synergistic mechanism of oxidative injury", by D. Yao, et al. Free Radical Biology and Medicine. 2005;39(10):1305-1309.
- Kallianpur AR. Genomic screening and complications of hematopoietic stem cell transplantation: has the time come? Bone Marrow Transplant. 2005;35(1):1-16.
Dr. Kallianpur’s team found that higher levels of the iron-delivery proteins heavy-chain ferritin and transferrin predict better cognitive outcomes in people with HIV, independent of factors like inflammation, over an extended period of follow-up.
Dr. Kallianpur’s team will investigate the role of iron in depression and cognitive impairment in people with HIV.
Dr. Kallianpur will investigate if kidney disease and cognitive impairment in people with HIV share an underlying mechanism and potentially highlight non-invasive biomarkers for these disorders.