Professor David D. Ho Director, Aaron Diamond AIDS Research Center Phone: 212-304-6102 Email: dh2994@cumc.columbia.edu Website: www.adarc.cuimc.columbia.edu/profile/david-d-ho-md

Professor David D. Ho
Director, Aaron Diamond AIDS Research Center
Phone: 212-304-6102
Email: dh2994@cumc.columbia.edu
Website: www.adarc.cuimc.columbia.edu/profile/david-d-ho-md

David D. Ho, M.D.

Professor of Microbiology & Immunology, Clyde '56 and Helen Wu Professor of Medicine and Director, Aaron Diamond AIDS Research Center
Member, National Academy of Medicine
Member, American Academy of Arts & Sciences
Fellow, American Association for the Advancement of Science
M.D., Harvard Medical School

Clinical virology, HIV pathogenesis, prevention of HIV and coronavirus transmission, HIV and coronavirus vaccine development

Research
The laboratory has been engaged in HIV research since the beginning of the AIDS pandemic, initially focusing on clinical virology and select topics in HIV pathogenesis. In the mid 1990s, the laboratory conducted a series of human studies to elucidate the dynamics of HIV replication in vivo. These studies formed the foundation for a pioneering effort to treat HIV “early and hard” and demonstrated for the first time the durable control of HIV replication in patients receiving combination antiretroviral therapy. This was the turning point in the AIDS pandemic, transforming an automatic death sentence into a manageable disease. 

For the past decade and a half, the laboratory has shifted its research focus to developing strategies to prevent HIV transmission. A protective vaccine against HIV remains elusive despite concerted research efforts. However, non-vaccine approaches to block HIV transmission have shown considerable promise. The laboratory was the first to demonstrate protective efficacy of a long-acting antiretroviral drug as pre-exposure prophylaxis in rhesus macaques. One such agent, cabotegravir, has been advanced into Phase-3 efficacy trials in high-risk populations, in collaboration with GlaxoSmithKline. In parallel, the laboratory has also engineered potent antibodies that neutralize divergent strains of HIV. The most promising neutralizing agent is a bispecific monoclonal antibody that entered a first-in-human clinical trial in 2019 with the support of the Bill & Melinda Gates Foundation.

During the COVID-19 pandemic, Dr. Ho’s previous experience as an adviser to governments in Beijing, Hong Kong, and Taipei during the 2002 – 2003 SARS epidemic led him to assemble a multi-disciplinary team of physicians, scientists and engineers at Columbia University that has identified one of the broadest and most potent panels of antibodies against SARS-CoV-2 to date. Several of these antibodies are currently in clinical development for the treatment and prevention of COVID-19. In addition to ongoing HIV research efforts, the Ho lab is continuing to investigate the pathogenesis and molecular mechanisms underlying SARS-CoV-2 infection in order to bring new solutions to the testing, treatment, and prevention of COVID-19.

The laboratory is funded by two NIH grants to pursue the use of engineered antibodies as a part of an international effort to purge the viral latent reservoir, and by the Jack Ma Foundation to work on coronavirus projects.

Please see our lab website for more information about our members and research.

 

Selected Publications

  1. Wang. Q, Guo, Y., Tam, A.R., Valdez, R., Gordon, A., Liu, L. and Ho, D.D. Deep immunological imprinting due to the ancestral spike in the current bivalent COVID-19 vaccine. Cell Rep. Med. 2023 [in press]

  2. Liu, L., Casner, R.G., Guo, Y., Wang, Q., Iketani, S., Chan, J.F., Yu, J., Dadonaite, B., Nair, M.S., Mohri, H., Reddem, E.R., Yuan, S., Poon, V.K., Chan, C.C., Yuen, K.Y., Sheng, Z., Huang, Y., Bloom, J.D., Shapiro, L. and Ho, D.D. Antibodies targeting a quaternary site on SARS-CoV-2 spike glycoprotein prevent viral receptor engagement by conformational locking. Immunity 2023 https://doi.org/10.1016/j.immuni.2023.09.003 [Online ahead of print]

  3. Duan, Y., Zhou, H., Liu, X., Iketani, S., Lin, M., Zhang, X., Bian, Q., Wang, H., Sun, H., Hong, S.J., Culbertson, B., Mohri, H., Luck, M.I., Zhu, Y., Liu, X., Lu, Y., Yang, X., Yang, K., Sabo, Y., Chavez, A., Goff, S.P., Rao, Z., Ho, D.D. and Yang, H. Molecular mechanisms of SARS-CoV-2 resistance to nirmatrelvir. Nature 2023 https://doi.org/10.1038/s41586-023-06609-0 [Online ahead of print]

  4. Wang, Q., Li, Z., Guo, Y., Mellis, I.A., Iketani, S., Liu, M., Yu, J., Valdez, R., Lauring, A.S., Sheng, Z., Gordon, A., Liu, L. and Ho, D.D. Evolving antibody evasion and receptor affinity of the Omicron BA.2.75 sublineage of SARS-CoV-2. iScience 2023 [in press]

  5. Tsuji, M., Nair, M.S., Masuda, K., Castagna, C., Chong, Z., Darling, T.L., Seehra, K., Hwang, Y., Ribeiro, A.L., Ferreira, G.M., Corredor, L., Alves Coelho-dos-Reis, J.G., Tsuji, Y., Mori, M., Boon, A.C.M., Diamond, M.S., Huang, Y. and Ho, D.D. An immunostimulatory glycolipid that blocks SARS-CoV-2, RSV, and influenza infections in vivo. Nature Comm. 2023; 14: 3959.

  6. Wang, Q., Iketani, S., Li, Z., Liu, L., Guo, Y., Huang, Y., Bowen, A.D., Liu, M., Wang, M., Yu, J., Valdez, R., Lauring, A.S., Sheng, Z., Wang, H.H., Gordon, A., Liu, L. and Ho, D.D. Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. Cell 2023; 186: 279-286. PMID: 36580913.

  7. Wang, Q., Bowen, A., Valdez, R., Gherasim, C., Gordon, A., Liu, L. and Ho, D.D. Antibody responses to Omicron BA.4-BA.5 bivalent booster. N. Engl. J. Med. 2023; 388: 567-569. PMID: 36630643.

  8. Iketani S, Mohri H, Culbertson B, Hong SJ, Duan Y, Luck MI, Annavajhala MK, Guo Y, Sheng Z, Uhlemann A-C, Goff SP, Sabo Y, Yang H, Chavez A and Ho DD. Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir. Nature 2023; 613: 558–564. https://doi.org/10.1038/s41586-022-05514-2

  9. Wang Q, Guo Y, Iketani S, Nair MS, Li Z, Mohri H, Wang M, Yu J, Bowen AD, Chang JY, Shah JG, Nguyen N, Chen Z, Meyers K, Yin MT, Sobieszczyk ME, Sheng Z, Huang Y, Liu L and Ho DD. Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1 BA.4 and BA.5. Nature 2022; 608: 603–608. https://doi.org/10.1038/s41586-022-05053-w

  10. Iketani S. Liu L, Guo Y, Liu L, Chan JF-W., Huang Y, Wang M, Luo Y, Yu J, Chu H, Chik KK-H, Yuen TT-T, Yin MT, Sobieszczyk ME, Huang Y, Yuen K-Y, Wang HH, Sheng Z and Ho DD. Antibody evasion properties of SARS-CoV-2 Omicron sublineages. Nature 2022; 604: 553–556. https://doi.org/10.1038/s41586-022-04594-4

  11. Liu L, Iketani S, Guo Y, Chan JFW, Wang M, Liu L, Luo Y, Chu H, Huang Y, Nair MS, Yu J, Chik KKH, Yuen TTT, Yoon C, To KKW, Chen H, Yin MT, Sobieszczyk ME, Huang Y, Wang HH, Sheng Z, Yuen KY and Ho DD. Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2. Nature 2022; 602: 676–681. https://doi.org/10.1038/s41586-021-04388-0

  12. Liu L, Iketani S, Guo Y, Casner RG, Reddem ER, Nair MS, Yu J, Chan JFW, Wang M, Cerutti G, Li Z, Castagna CD, Corredor L, Chu H, Yuan S, Poon VKM, Chan CCS, Chen Z, Luo Y, Cunningham M, Chavez A, Yin MT, Perlin DS, Tsuji M, Yuen KY, Kwong PD, Sheng Z, Huang Y, Shapiro L and Ho DD. Isolation and comparative analysis of antibodies that broadly neutralize sarbecoviruses. Sci. Transl. Med. 2021. In press.

  13. Kissler SM, Fauver JR, Mack C, Tai CG, Breban MI, Watkins AE, Samant RM, Anderson DJ, Metti J, Khullar G, Baits R, MacKay M, Salgado D, Baker T, Dudley JT, Mason CE, Ho DD, Grubaugh ND and Grad YH. Viral dynamics of SARS-CoV-2 variants in vaccinated and unvaccinated individuals. N. Engl. J. Med. 2021; 355: 2489-2491.

  14. Wang P, Casner RG, Nair MS, Wang M, Yu J, Cerutti G, Liu L, Kwong PD, Huang Y, Shapiro L and Ho DD. Increased resistance of SARS-CoV-2 variant P.1 to antibody neutralization. Cell Host & Microbe 2021; 29: 747-751.

  15. Annavajhala MK, Mohri H, Zucker JE, Sheng Z, Wang P, Gomez-Simmonds A, Ho DD and Uhlemann AC. A novel SARS-CoV-2 variant of concern, B.1.526, identified in New York. Nature 2021; 597: 703-708.

  16. Wang P, Nair MS, Liu L, Iketani S, Luo Y, Guo Y, Wang M, Yu J, Zhang B, Kwong PD, Graham BS, Mascola JR, Chang JY, Yi MT, Sobieszczyk M, Kyratsous CA, Shapiro L, Sheng Z, Nair MS, Huang Y and Ho DD. Increased resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 to antibody neutralization. Nature 2021; 593: 130-135.

  17. Iketani S, Forouhar F, Liu H, Hong SJ, Lin FY, Nair M, Zask A, Huang Y, Xing L, Stockwell BR, Chavez A and Ho DD. Lead compounds for the development of SARS-CoV-2 3CL protease inhibitors. Nature Communications 2021; 12: 2708.

  18. Liu L, Wang P, Nair MS, Yu J, Huang Y, Rapp MA, Wang Q, Luo Y, Sahi V, Figueroa A, Guo XV, Cerutti G, Bimela J, Gorman J, Zhou T, Kwong PD, Sodroski JG, Yin MT, Sheng Z, Shapiro L and Ho DD. Potent neutralizing monoclonal antibodies directed to multiple epitopes on the SARS-CoV-2 spike. Nature 2020; 584: 450-456.

  19. Wang P, Gajjar MR, Yu J, Padte NN, Gettie A, Blanchard JL, Russell-Rodrique K, Liao LE, Perelson AS, Huang Y, and Ho DD. Quantifying the contribution of Fc-mediated effector functions to the antiviral activity of of anti-HIV-1 antibodies in vivo. Proc. Natl. Acad. Sci. 2020; 117: 18002-18009.

  20. Huang Y, Yu J, Lanzi A, Andrews CD, Yao X, Sun M, Seaman MS, Padte NN and Ho DD. Engineered bispecific antibodies with exquisite HIV-1 neutralizing activity. Cell 2016; 165: 1621-1631.

  21. Andrews CD, Yueh YL, Spreen WR, Bernard LS, Boente-Carrera M, Rodriguez K, Gettie A, Russell-Lodrigue K, Blanchard J, Ford S, Mohri H, Cheng-Mayer C, Hong Z, Ho DD and Markowitz M. Long-acting integrase inhibitor protects female macaques from repeated high-dose intravaginal SHIV challenges. Science Transl. Med. 2015; 7: 270ra4.

  22. Andrews CD, Spreen WR, Mohri H, Moss L, Ford S, Gettie A, Russell-Lodrique K, Bohm RP, Cheng-Mayer C, Hong Z, Markowitz M and Ho DD. Long-acting integrase inhibitor protects macaques from intrarectal simian/human immunodeficiency virus. Science 2014; 343: 1151-1154.

  23. Song R, Oren DA, Franco D, Seaman MS, Ho DD.Strategic addition of an N-linked glycan to a monoclonal antibody improves its anti-HIV-1-neutralizing activity. Nature Biotech. 2013; 31: 1047-1053.

  24. Pace CS, Song R, Ochsenbauer C, Andrews, CD, Franco D, Yu J, Oren DA, Seaman MS and Ho DD. Bispecific antibodies directed to CD4 domain 2 and HIV envelope exhibit exceptional breadth and picomolar potency against HIV-1. Proc. Natl. Acad. Sci. 2013; 110: 13540-13545.

  25. Chen MW, Cheng T-J R, Huang Y, Jan J-T, Ma S-H, Yu AL, Wong C-H, and Ho DD. A consensus-hemagglutinin-based DNA vaccine that protects mice against divergent H5N1 influenza viruses. Proc. Natl. Acad. Sci. USA 2008; 105: 13538-13543.

  26. Lu L, Jia M, Ma Y, Yang L, Chen Z, Ho DD, Jiang Y, Zhang L. The changing face of HIV in China. Nature 2008; 455:609-611. Chen HY, Di Mascio M, Perelson AS, Ho DD and Zhang L. Determination of virus burst size in vivo using a single-cycle SIV in rhesus macaques. Proc. Natl. Acad. Sci. USA 2007; 104: 19079-19084.

  27. Zhang L, Yu, W, He T, Yu J, Caffrey RE, Dalmasso EA, Fu S, Pham T, Mei J, Ho JJ, Zhang W, Lopez P and Ho DD. Contribution of human alpha-defensins-1, -2, and -3 to the anti-HIV-1 activity of CD8 antiviral factor. Science 2002; 298: 995-1000.

  28. Mohri H, Perelson AS, Tung K, Ribeiro R, Ramratnam B, Markowitz M, Kost R, Hurley A, Weinberger L, Cesar D, Hellerstein MK and Ho DD. Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy. J. Exp. Med. 2001; 194: 1277-1287.

  29. Ramratnam B, Mittler JE, Zhang L, Boden D, Hurley A, Fang F, Macken CA, Perelson AS, Markowitz M and Ho DD. The decay of the latent reservoir of replication-competent HIV-1 is inversely correlated with the extent of residual viral replication during prolonged antiretroviral therapy. Nature Med. 2000; 6: 76-81.

  30. Zhang L, Lewin S, Markowitz M, Lin H-H, Skulsky E, Karanicolas R, He Y, Jin X, Tuttleton S, Vesanen M, Spiegel H, Kost R, J. van Lunzen, H-J. Stellbrink, Wolinsky S, Borkowsky W, Palumbo P, Kostrikis LG and Ho DD. Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy. J. Exp. Med. 1999; 190: 725-732.

  31. Jin X, Bauer DE, Tuttleton SE, Lewin S, Gettie A, Kostrikis L, Blanchard J, Irwin CE, Safrit JT, Zhang L and Ho DD. Dramatic rise in plasma viremia after CD8+ T-cell depletion in simian immunodeficiency virus-infected macaques. J. Exp. Med. 1999; 189: 991-998.

  32. Zhang L, Ramratnam B, Tenner-Racz, He Y, Vesanen M, Lewin S, Talal A, Racz P, Perelson AS, Korber BT, Markowitz M and Ho DD. Quantifying residual HIV-1 replication in patients receiving effective combination antiretroviral therapy. N. Engl. J. Med. 1999; 340: 1605-1613.

  33. Kostrikis LG, Huang Y, Moore JP, Wolinsky SM, Zhang L, Guo Y, Deutsch L, Phair J, Neumann AU and Ho DD. A chemokine receptor CCR2 allele delays HIV-1 disease progression and is associated with a CCR5 promoter mutation. Nature Med. 1998; 4: 350-353.

  34. Mohri H, Bonhoeffer S, Monard S, Perelson AS and Ho DD. Rapid turnover of T lymphocytes in SIV-infected rhesus macaques. Science 1998; 279: 1223-1227.

  35. Zhu T, Korber BT, Nahmias AJ, Hooper E, Sharp PM and Ho DD. An African HIV-1 sequence from 1959 and implications for the origin of the epidemic. Nature 1998; 391: 594-597.

  36. Perelson AS, Essunger P, Cao Y, Vesanen M, Hurley A, Saksela K, Markowitz M and Ho DD. Decay characteristics of HIV-1-infected compartments during combination therapy. Nature 1997; 87: 188-191.

  37. Huang Y, Paxton WA, Wolinsky SM, Neumann AU, Zhang L, He T, Kang S, Ceradini D, Jin Z, Yazdanbakhsh K, Kunstman K, Erickson D, Dragon E, Landau N, Phair J, Ho DD and Koup RA. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nature Med. 1996; 2: 1240-1243.

  38. Perelson AS, Neumann AU, Markowitz M, Leonard J and Ho DD. HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science 1996; 271: 1582-1586.

  39. Markowitz M, Saag M, Powderly W, Hurley AM, Hsu A, Valdes JM, Henry D, Sattler F, La Marca A, Leonard JM and Ho DD. Clinical evaluation of the safety and efficacy of ritonavir (ABT-538), an inhibitor of HIV-1 protease. N. Engl. J. Med. 1995; 333: 1534-1539.

  40. Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM and Markowitz M. Rapid turnover of plasma virion and CD4 lymphocytes in HIV-1 infection. Nature 1995; 373: 123-126.

  41. Cao Y, Qing L, Zhang GL, Safrit J and Ho DD. Virological and immunological characterization of long-term survivors of HIV-1 infections. N. Engl. J. Med. 1995; 332: 201-208.

  42. Zhu T, Mo H, Wang N, Nam DS, Cao Y, Koup R and Ho DD. Genotypic and phenotypic characterization of HIV-1 in patients with primary infection. Science 1993; 261: 1179-1181.

  43. Ho DD, Cao Y, Zhu T, Farthing C, Wang N, Gu G, Schooley RT and Daar ES. Idiopathic CD4+ T-lymphocytopenia (ICL): immunodeficiency without evidence of human immunodeficiency virus infection. N. Engl. J. Med. 1993; 328: 380-385.

  44. Daar ES, Moudgil T, Meyer RD and Ho DD. Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection. N. Engl. J. Med. 1991; 324: 961-964.

  45. Ho DD, Moudgil T and Alam M. Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. N. Engl. J. Med. 1989; 321: 1621-1625.

  46. Melish ME, Marchette NJ, Kaplan JC, Kihara S, Ching D and Ho DD. Absence of significant RNA-dependent DNA polymerase activity in lymphocytes from patients with Kawasaki syndrome. Nature 1989; 337: 288-290.