Ping An, M.D., MPH
Ping  An, MD, MPH
Staff Scientist (Contr)

Dr. An's primary interest is uncovering host genetic factors that confer resistance or susceptibility to common infectious diseases including human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV). Current projects include: (1) identifying host genetic resistance/susceptibility factors to HIV-1 acquisition and AIDS progression in HIV natural history cohorts, and (2) identifying host genetic factors that confer resistance/susceptibility to HBV infection and hepatocellular carcinoma. By performing a genetic association study and functional genetic analyses, his work has led to identification and characterization of several human genetic factors that influence HIV-1 and HBV infection.

Areas of Expertise
1) host genetic factors of HIV infection, 2) host genetics of HBV infection, 3) virus-host interactions, 4) genetic epidemiology, 5) population genetics, 6) hepatocellular carcinoma

Contact Info

Ping An, M.D., MPH
Center for Cancer Research
National Cancer Institute
Building 560, Room 11-84
Frederick, MD 21701-1201
301-846-5932
anp@mail.nih.gov

Dr. An's primary interest is to uncover the genetic factors that confer host resistance or susceptibility to common infectious pathogens, especially human immunodeficiency virus type 1 (HIV-1), hepatitis B virus (HBV), and hepatitis C virus (HCV).

Individuals' responses to invading pathogens vary, ranging from complete resistance to increased susceptibility. The infection and progression of infectious diseases depend on ecological and environmental factors as well as host genetic factors. Genetic restriction/susceptibility factors to viral diseases are the result of the interaction of virus and host defense that developed during human evolution. Uncovering the genetic association may lead to the identification of host factors that play key roles in determining the outcome of virus-host interactions.

Dr. An's work focuses on identifying the human genetic components that influence disease susceptibility by using a population genetics epidemiology approach, in combination with evolutionary and functional analyses. A great number of host factors interact with HIV-1; however, their relative contribution is not clear due to complex interaction. Population genetics association studies provide a way to assess the final impact of genes on disease outcome and to  identify the most critical genes involved in pathogenesis.

To identify the host genetic factors associated with HIV-1/AIDS, we make use of five large U.S.-based HIV-1 longitudinal cohorts, which were assembled before an effective anti-HIV treatment was available. The participants include those at high risk of being exposed to HIV-1 but who are uninfected (HREU), and those who become infected during the course of the study (seroconverters, SC) whose time of infection and progression to a particular AIDS outcome is known. The frequency distribution of genetic variants in HREU and SC is then compared to assess their impact on the participant's risk of acquiring HIV-1 infection. A survival analysis is applied to assess the role of these variants on disease progression from the time of the initial HIV infection to AIDS outcomes: CD4 cell <200, AIDS-defining conditions, and AIDS-related death. Recently, using a candidate gene approach that focused on the regulation pathways of the HIV-1 life cycle, host immune response, and innate defense, we have identified several genetic factors that influence HIV-1/AIDS.

1) Chemokine and chemokine receptors, including RANTES, IFNG, chemokine gene clusters, and chemokine receptor gene clusters. An intronic variant and its haplotype in RANTES, encoding a chemokine that blocks CCR5, was found to affect gene regulation and AIDS progression; a functional promoter variant in IFNG was shown to influence AIDS progression; a cluster of chemokine genes on 17q12 was associated with an altered rate of AIDS progression; a cluster of chemokine receptor gene loci on 3p21 was also associated with AIDS progression.

2) Innate immunity factors, including TRIM5, APOBEC3G, and CUL5. Certain regulatory and nonsynonymous variants in TRIM5, whose rhesus version confers complete restriction to HIV-1, were found to affect human susceptibility to HIV-1 infection. A nonsynonymous variant in APOBEC3G, encoding a protein that intrinsically restricts HIV-1, was identified as accelerating disease progression. The variants and haplotype clusters in CUL5, encoding a protein that helps HIV-1 vif degrade APOBEC3G, were associated with CD4 cell depletion in HIV-1-infected individuals.

Dr. An is also studying the host genetic factors that contribute to infection by HBV and HCV.

Scientific Focus Areas:
Epidemiology, Genetics and Genomics, Virology
Selected Recent Publications
  1. Regulatory variation in HIV-1 dependency factor ZNRD1 associates with host resistance to HIV-1 acquisition.
    An P, Goedert JJ, Donfield S, Buchbinder S, Kirk G, Detels R, Winkler CA.
    J Infect Dis. 210: 1539-48, 2014. [ Journal Article ]
  2. An P, Winkler C, Guan L, O'Brien SJ, Zeng Z.
    J. Infect. Dis. 203: 943-7, 2011. [ Journal Article ]
  3. Troyer JL, Nelson GW, Lautenberger JA, Chinn L, McIntosh C, Johnson RC, Sezgin E, Kessing B, Malasky M, Hendrickson SL, Li G, Pontius J, Tang M, An P, Winkler CA, Limou S, Le Clerc S, Delaneau O, Zagury JF, Schuitemaker H, van Manen D, Bream JH, Gomperts ED, Buchbinder S, Goedert JJ, Kirk GD, O'Brien SJ.
    J. Infect. Dis. 203: 1491-502, 2011. [ Journal Article ]
  4. Polymorphisms of CUL5 are associated with CD4+ T cell loss in HIV-1 infected individuals .
    An P, Duggal P, Wang LH, O’Brien SJ, Donfield S, Goedert JJ, Phair J, Buchbinder S, Kirk GD, Winkler CA.
    PLoS Genet. 3 : e19, 2007. [ Journal Article ]
  5. Nelson GW, Freedman BI, Bowden DW, Langefeld CD, An P, Hicks PJ, Bostrom MA, Johnson RC, Kopp JB, Winkler CA.
    Hum. Mol. Genet. 19: 1805-15, 2010. [ Journal Article ]

Dr. An obtained his medical degree from Lanzhou University, China, followed by specialty training in infectious diseases. He received his MPH from the Johns Hopkins University Bloomberg School of Public Health in Baltimore, MD, with a concentration in genetic epidemiology. Dr. An undertook his postdoctoral research in the Laboratory of Genomic Diversity, NCI. Since 1998, Dr. An has been a staff scientist in Dr. Cheryl Winkler's Molecular Genetic Epidemiology Studies Section, investigating the role of host genetics in susceptibility and resistance to infectious diseases, including human immunodeficiency virus type 1 (HIV-1) and the hepatitis virus.

Research

Dr. An's primary interest is to uncover the genetic factors that confer host resistance or susceptibility to common infectious pathogens, especially human immunodeficiency virus type 1 (HIV-1), hepatitis B virus (HBV), and hepatitis C virus (HCV).

Individuals' responses to invading pathogens vary, ranging from complete resistance to increased susceptibility. The infection and progression of infectious diseases depend on ecological and environmental factors as well as host genetic factors. Genetic restriction/susceptibility factors to viral diseases are the result of the interaction of virus and host defense that developed during human evolution. Uncovering the genetic association may lead to the identification of host factors that play key roles in determining the outcome of virus-host interactions.

Dr. An's work focuses on identifying the human genetic components that influence disease susceptibility by using a population genetics epidemiology approach, in combination with evolutionary and functional analyses. A great number of host factors interact with HIV-1; however, their relative contribution is not clear due to complex interaction. Population genetics association studies provide a way to assess the final impact of genes on disease outcome and to  identify the most critical genes involved in pathogenesis.

To identify the host genetic factors associated with HIV-1/AIDS, we make use of five large U.S.-based HIV-1 longitudinal cohorts, which were assembled before an effective anti-HIV treatment was available. The participants include those at high risk of being exposed to HIV-1 but who are uninfected (HREU), and those who become infected during the course of the study (seroconverters, SC) whose time of infection and progression to a particular AIDS outcome is known. The frequency distribution of genetic variants in HREU and SC is then compared to assess their impact on the participant's risk of acquiring HIV-1 infection. A survival analysis is applied to assess the role of these variants on disease progression from the time of the initial HIV infection to AIDS outcomes: CD4 cell <200, AIDS-defining conditions, and AIDS-related death. Recently, using a candidate gene approach that focused on the regulation pathways of the HIV-1 life cycle, host immune response, and innate defense, we have identified several genetic factors that influence HIV-1/AIDS.

1) Chemokine and chemokine receptors, including RANTES, IFNG, chemokine gene clusters, and chemokine receptor gene clusters. An intronic variant and its haplotype in RANTES, encoding a chemokine that blocks CCR5, was found to affect gene regulation and AIDS progression; a functional promoter variant in IFNG was shown to influence AIDS progression; a cluster of chemokine genes on 17q12 was associated with an altered rate of AIDS progression; a cluster of chemokine receptor gene loci on 3p21 was also associated with AIDS progression.

2) Innate immunity factors, including TRIM5, APOBEC3G, and CUL5. Certain regulatory and nonsynonymous variants in TRIM5, whose rhesus version confers complete restriction to HIV-1, were found to affect human susceptibility to HIV-1 infection. A nonsynonymous variant in APOBEC3G, encoding a protein that intrinsically restricts HIV-1, was identified as accelerating disease progression. The variants and haplotype clusters in CUL5, encoding a protein that helps HIV-1 vif degrade APOBEC3G, were associated with CD4 cell depletion in HIV-1-infected individuals.

Dr. An is also studying the host genetic factors that contribute to infection by HBV and HCV.

Scientific Focus Areas:
Epidemiology, Genetics and Genomics, Virology

Publications

Selected Recent Publications
  1. Regulatory variation in HIV-1 dependency factor ZNRD1 associates with host resistance to HIV-1 acquisition.
    An P, Goedert JJ, Donfield S, Buchbinder S, Kirk G, Detels R, Winkler CA.
    J Infect Dis. 210: 1539-48, 2014. [ Journal Article ]
  2. An P, Winkler C, Guan L, O'Brien SJ, Zeng Z.
    J. Infect. Dis. 203: 943-7, 2011. [ Journal Article ]
  3. Troyer JL, Nelson GW, Lautenberger JA, Chinn L, McIntosh C, Johnson RC, Sezgin E, Kessing B, Malasky M, Hendrickson SL, Li G, Pontius J, Tang M, An P, Winkler CA, Limou S, Le Clerc S, Delaneau O, Zagury JF, Schuitemaker H, van Manen D, Bream JH, Gomperts ED, Buchbinder S, Goedert JJ, Kirk GD, O'Brien SJ.
    J. Infect. Dis. 203: 1491-502, 2011. [ Journal Article ]
  4. Polymorphisms of CUL5 are associated with CD4+ T cell loss in HIV-1 infected individuals .
    An P, Duggal P, Wang LH, O’Brien SJ, Donfield S, Goedert JJ, Phair J, Buchbinder S, Kirk GD, Winkler CA.
    PLoS Genet. 3 : e19, 2007. [ Journal Article ]
  5. Nelson GW, Freedman BI, Bowden DW, Langefeld CD, An P, Hicks PJ, Bostrom MA, Johnson RC, Kopp JB, Winkler CA.
    Hum. Mol. Genet. 19: 1805-15, 2010. [ Journal Article ]

Biography

Dr. An obtained his medical degree from Lanzhou University, China, followed by specialty training in infectious diseases. He received his MPH from the Johns Hopkins University Bloomberg School of Public Health in Baltimore, MD, with a concentration in genetic epidemiology. Dr. An undertook his postdoctoral research in the Laboratory of Genomic Diversity, NCI. Since 1998, Dr. An has been a staff scientist in Dr. Cheryl Winkler's Molecular Genetic Epidemiology Studies Section, investigating the role of host genetics in susceptibility and resistance to infectious diseases, including human immunodeficiency virus type 1 (HIV-1) and the hepatitis virus.