Click here for a more complete description of Dr. Allen's lab and research interests.

3 post-doctoral fellows, 4 research technicians, 1 lab manager

My laboratory is primarily investigating the impact that viral sequence diversity has on immune control in the setting of HIV-1 infection. Cellular CD8+ T cell responses (CTL) represent a critical arm of the immune response in the control of HIV-1 infections. The ability of HIV to rapidly evolve and escape from these responses within a host, combined with the enormous sequence diversity of HIV strains worldwide, is one of the largest hurdles facing an AIDS vaccine. Unfortunately, we still lack a thorough understanding of the impact that viral escape from these responses has on immune control.

My laboratory employs full length viral genome sequencing of HIV in acute and chronic HIV infected subjects to identify the extent to which HIV is capable of evading host immune responses over the course of infection, and the degree to which such forces are shaping HIV sequence evolution on the global level. Extensions of this work are now characterizing the boundaries by which HIV sequence evolution is restricted by protein structure and function by investigating whether particular mutations are capable of compromising the replicative fitness of HIV and thus contributing to immune control.  Similarly, my lab is exploring issues of viral escape and replication in the setting of hepatitis C virus (HCV), another highly variable virus whose infections are also endemic in the human population. These studies are designed to aid in the development of effective vaccines against HIV and HCV though a better understanding of the routes by which these pathogens compromise host immune defenses and evolve on the global level. Finally, in collaboration with the Chulalongkorn Medical Research Center in Bangkok, Thailand we are characterizing immune responses and viral sequence evolution in a population where highly unique strains of HIV are circulating.

Important Past Accomplishments:

1. Characterizing the role of immune pressures in shaping the sequence diversity of HIV.
2. Identifying the role of HIV superinfection in loss of immune control and disease progression.
3. Characterizing the role of sequence constraints on reversion of transmitted mutations in HIV.
4. Development of a flow-based reporter system to measure replication of primary HIV strains.

1. Determining the impact of CTL escape mutations on immune control following acute HIV infection.
2. Defining the extent of HLA-class I associated (CTL escape) sequence polymorphisms across the HIV and HCV proteomes.
3. Examining the role of viral replication capacity on immune control of HIV.
4. Determining the impact of CTL escape mutations on viral replicative fitness.
5. Studying the contribution of viral sequence variation to HIV superinfection. .

Publications of Interest:

1. Timm J, Li B, Daniels MG, Bhattacharya T, Reyor LL, Allgaier R, Kuntzen T, Fischer W, Duncan J, Schulze zur Wiesch J, Kim AK, Frahm N, Brander C, Chung RT, Lauer GM, Korber BT, Allen TM HLA-Associated Sequence Polymorphisms in HCV Reveal Reproducible Immune Responses and Constraints on Viral Evolution.  Hepatology, In Press.
   
2. Altfeld M, Allen TM.  Hitting HIV Where it Hurts: An Alternative Approach to HIV Vaccine Design
   Trends Immunol. 2006 Nov 27(11) 504-510.
3. Li B, Gladden AD, Altfeld M, Kaldor JM, Cooper DA, Kelleher AD, Walker BD, Allen TM.  Rapid Reversion of Sequence Polymorphisms Dominates Early HIV-1 Evolution.  J Virol. 2007 Jan;81(1):193-201. 
4. Brockman MA, Tanzi GO, Walker BD, Allen TM.  Use of a Novel GFP Reported Cell Line to Examine Replication Capacity of CXCR4- and CCR5-tropic HIV-1 by Flow Cytometry.  J Virol Methods. 2006 131(2):134-42.
5. Allen TM, Altfeld M, Geer SC, Kalife ET, Moore C, O’Sullivan KM, DeSouza I, Feeney ME, Eldridge RL, Maier EL, Kaufmann DE, Lahaie MP, Reyor L, Tanzi G, Johnston MN, Brander C, Draenert R, Rockstroh JK, Jessen H, Rosenberg ES, Mallal SA, Walker BD.  Selective Escape from CD8+ T Cell Responses Represents a Major Driving Force of HIV-1 Sequence Diversity And Reveals Constraints on HIV-1 Evolution.  J. Virol. 2005;79 13239-13249.
6. Timm J, Lauer GM, Kavanagh DG, Sheridan I, Kim AY, Lucas M, Pillay T, Ouchi K, Reyor LL, Zur Wiesch JS, Gandhi RT, Chung RT, Bhardwaj N, Klenerman P, Walker BD, Allen TM.   CD8 epitope escape and reversion in acute HCV infection.   J Exp Med. 2004 Dec 20;200(12): 1593-604.
7. Altfeld M*, Allen TM*, Yu XG, Johnston MN, Agrawal D, Korber BT, Montefiori DC, O'Connor DH, Davis BT, Lee PK, Maier EL, Harlow J, Goulder PJ, Brander C, Rosenberg ES, Walker BD.   HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus.   Nature. 2002 Nov 28;420(6914):434-9. (shared 1st author)
8. O'Connor DH*, Allen TM*, Vogel TU, Jing P, DeSouza IP, Dodds E, Dunphy EJ, Melsaether C, Mothé B, Yamamoto H, Horton H, Wilson N, Hughes AL, Watkins DI.  Acute phase cytotoxic T lymphocyte escape is a hallmark of simian immunodeficiency virus infection.  Nature Medicine 2002 May;8(5):493-9. (shared 1st author)
9. Allen TM, O'Connor DH, Jing P, Dzuris JL, Mothé BR, Vogel TU, Dunphy E, Liebl ME, Emerson C, Wilson N, Kunstman KJ, Wang X, Allison DB, Hughes AL, Desrosiers RC, Altman JD, Wolinsky SM, Sette A, Watkins DI.   Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia.   Nature. 2000 Sep 21;407(6802):386-90.

Additional Information

For additional information contact:
Todd Allen, Ph.D.
Assistant Professor in Medicine
Partners AIDS Research Center
Massachusetts General Hospital
Harvard Medical School
Bldg. 149, 13th Street, Rm 6616
Charlestown, MA 02129
Phone 617 726-7846
Fax 617 726-5411
tallen2@partners.org