Ping  An, MD, MPH
Ping An, MD, MPH
Staff Scientist (Contr)

Center for Cancer Research
National Cancer Institute

Building 560, Room 11-84
Frederick, MD 21701-1201
301-846-5932

Dr. An's primary interest is to uncover the genetic factors that confer host resistance or susceptibility to common infectious pathogens, especially 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 the ecological and environmental factors as well as host genetic factors. Genetic restriction/susceptibility factors to viral diseases were the result of the interaction of virus and host defense developed during human evolutionary. Uncovering genetic association may lead to the identification of the 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 the disease susceptibility by using a population genetic epidemiology approach, in combination with evolutionary and functional analysis

Areas of Expertise
HIV-1, HBV, HCV

Dr. An's primary interest is to uncover the genetic factors that confer host resistance or susceptibility to common infectious pathogens, especially 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 the ecological and environmental factors as well as host genetic factors. Genetic restriction/susceptibility factors to viral diseases were the result of the interaction of virus and host defense developed during human evolutionary. Uncovering genetic association may lead to the identification of the 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 the disease susceptibility by using a population genetic epidemiology approach, in combination with evolutionary and functional analysis. A great number of host factors interact with HIV-1; however, their relative contribution is not clear due to complex interaction. Population genetic association study provides a way to assess the genes final impact on the 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 US-based HIV-1 longitudinal cohorts, which were assembled before the effective anti-HIV treatment was available. The participants included those high risk exposed to HIV-1 but uninfected (HREU) and those that become infected during the study (seroconverters, SC) whose time of infection and progression to particular AIDS outcome is known.

The frequency distribution of genetic variants in HREU and SC is compared to assess the impact on the risk of acquiring HIV-1 infection. The survival analysis is applied to assess the role of variants on disease progression from the time since HIV infection to AIDS outcomes: CD4 cell <200, AIDS defining conditions and AIDS-related death. Recently, with a candidate gene approach focusing on factors in the pathways of the regulation of 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 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 restrict HIV-1, was identified to accelerate disease progression. The variants and haplotype clusters in CUL5, encoding a protein that help HIV-1 vif degrade APOBEC3G, was associated with CD4 cell depletion in HIV-1 infected individuals.

Dr. An is also studying the host genetic factors contributing to the infection of HBV and HCV.

Selected Publications
  1. An P, Winkler C, Guan L, O'Brien SJ, Zeng Z.
    J. Infect. Dis.. 203: 943-7, 2011. [ Journal Article ]
  2. Madlala P, Gijsbers R, Christ F, Hombrouck A, Werner L, Mlisana K, An P, Abdool Karim SS, Winkler CA, Debyser Z, Ndung'u T.
    AIDS. 25: 1711-9, 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. An P, Li R, Wang JM, Yoshimura T, Takahashi M, Samudralal R, O'Brien SJ, Phair J, Goedert JJ, Kirk GD, Troyer JL, Sezgin E, Buchbinder SP, Donfield S, Nelson GW, Winkler CA.
    PLoS Genet.. 7: e1002328, 2011. [ 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 on 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. He undertook his postdoctoral research in the Laboratory of Genomic Diversity, National Cancer Institute. Since 1998, Dr. An has been a staff scientist in the Molecular Genetic Epidemiology Section, investigating the role of host genetics in susceptibility and resistance to infectious diseases including HIV-1 and hepatitis virus.

Summary

Dr. An's primary interest is to uncover the genetic factors that confer host resistance or susceptibility to common infectious pathogens, especially 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 the ecological and environmental factors as well as host genetic factors. Genetic restriction/susceptibility factors to viral diseases were the result of the interaction of virus and host defense developed during human evolutionary. Uncovering genetic association may lead to the identification of the 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 the disease susceptibility by using a population genetic epidemiology approach, in combination with evolutionary and functional analysis

Areas of Expertise
HIV-1, HBV, HCV

Research

Dr. An's primary interest is to uncover the genetic factors that confer host resistance or susceptibility to common infectious pathogens, especially 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 the ecological and environmental factors as well as host genetic factors. Genetic restriction/susceptibility factors to viral diseases were the result of the interaction of virus and host defense developed during human evolutionary. Uncovering genetic association may lead to the identification of the 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 the disease susceptibility by using a population genetic epidemiology approach, in combination with evolutionary and functional analysis. A great number of host factors interact with HIV-1; however, their relative contribution is not clear due to complex interaction. Population genetic association study provides a way to assess the genes final impact on the 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 US-based HIV-1 longitudinal cohorts, which were assembled before the effective anti-HIV treatment was available. The participants included those high risk exposed to HIV-1 but uninfected (HREU) and those that become infected during the study (seroconverters, SC) whose time of infection and progression to particular AIDS outcome is known.

The frequency distribution of genetic variants in HREU and SC is compared to assess the impact on the risk of acquiring HIV-1 infection. The survival analysis is applied to assess the role of variants on disease progression from the time since HIV infection to AIDS outcomes: CD4 cell <200, AIDS defining conditions and AIDS-related death. Recently, with a candidate gene approach focusing on factors in the pathways of the regulation of 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 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 restrict HIV-1, was identified to accelerate disease progression. The variants and haplotype clusters in CUL5, encoding a protein that help HIV-1 vif degrade APOBEC3G, was associated with CD4 cell depletion in HIV-1 infected individuals.

Dr. An is also studying the host genetic factors contributing to the infection of HBV and HCV.

Publications

Selected Publications
  1. An P, Winkler C, Guan L, O'Brien SJ, Zeng Z.
    J. Infect. Dis.. 203: 943-7, 2011. [ Journal Article ]
  2. Madlala P, Gijsbers R, Christ F, Hombrouck A, Werner L, Mlisana K, An P, Abdool Karim SS, Winkler CA, Debyser Z, Ndung'u T.
    AIDS. 25: 1711-9, 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. An P, Li R, Wang JM, Yoshimura T, Takahashi M, Samudralal R, O'Brien SJ, Phair J, Goedert JJ, Kirk GD, Troyer JL, Sezgin E, Buchbinder SP, Donfield S, Nelson GW, Winkler CA.
    PLoS Genet.. 7: e1002328, 2011. [ 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 on 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. He undertook his postdoctoral research in the Laboratory of Genomic Diversity, National Cancer Institute. Since 1998, Dr. An has been a staff scientist in the Molecular Genetic Epidemiology Section, investigating the role of host genetics in susceptibility and resistance to infectious diseases including HIV-1 and hepatitis virus.