research associate professor
research associate professor
Ph.D., Penn State College of Medicine
Fields of Interest
NeuroAIDS pathogenesis, HIV/SIV peripheral neuropathy, osteopontin, monocytes/macrophages.
My research has examined the pathogenesis of central nervous system (CNS) diseases, focusing on neuroAIDS resulting from human immunodeficiency (HIV) and the non-human primate equivalent simian immunodeficiency (SIV) infection. I have specifically been interested in the viral and cellular interactions that lead to the disruption of cellular function in neuroAIDS.
My doctoral dissertation research was performed at the Penn State College of Medicine under the guidance of Dr. Brian Wigdahl. During this time, I examined the molecular mechanisms involved in HIV-associated dementia. My focus was the interaction of the cellular protein C/EBP and viral protein R, Vpr, with the HIV long terminal repeat (LTR) and the effect of sequence variation on this interaction. The HIV LTR drives the expression for the entire viral sequence and changes in its interaction may alter replication and disease progression.
For my postdoctoral fellowship, I joined the laboratory of Dr. Howard Fox at the Scripps Research Institute and focused on immune regulation and induction of osteopontin in macrophages and their contribution to neurological disease. One of my main foci was the examination of the mechanisms of monocyte accumulation in the brain during neuroAIDS. This work was critical because monocytes are a major target of the HIV and SIV and also serve as carriers of virus into the brain, where they help maintain viral persistence. We have shown that osteopontin prevents monocyte recirculation and apoptosis and is highly increased in HIV-associated dementia.
My current research focus at Boston College uses these experiences, and I will continue utilizing the non-human primate model of neuroAIDS to examine the role of monocyte/macrophages as viral reservoirs, and the effect of drug therapies in clearing anatomic and histologic reservoirs. In addition, I am beginning to develop an animal model of HIV associated peripheral neuropathy to study the relative roles of virus and activated resident and circulating macrophages in producing dorsal root ganglion cell damage and/or damage to the long sensory tracts in the spinal cord.
NIH/NINDS R01 NS082116-01
“Monocyte/macrophage traffic and peripheral nerve pathogenesis”
9-30-12 to 6-30-2017
Subramanian S, Tawakol A, Burdo TH, Abbara S, Wei J, Vijayakumar J, Corsini E, Abdelbaky A, Zanni MV, Hoffmann U, Williams KC, Lo J, Grinspoon SK. Arterial inflammation in patients with HIV. JAMA. 2012 Jul 25;308(4):379-86. With Editorial Commentary.
Strickland SL, Gray RR, Lamers S, Burdo TH, Huenink E, Nolan D, Nowlin B, Alvarez X, Midkiff C, Goodenow M, Williams K, Salemi M. Efficient Transmission and Persistence of Low Frequency SIVmac251 Variants in CD8-depleted Rhesus Macaques with Different Neuropathology. J Gen Virol. 2012 Feb 1.
Burdo TH, Orzechowski K, Knight HL, Miller AD, Williams KC. Dorsal root ganglia damage in SIV-infected rhesus macaques: An animal model of HIV-induced sensory neuropathy. Am J Pathol. 2012 Apr;180(4):1362-9.
Williams K and Burdo TH. Monocyte Mobilization, Activation Markers, and Unique Macrophage Populations in the Brain: Observations From SIV infected Monkeys Are Informative With Regard to Pathogenic Mechanisms of HIV Infection in Humans. Journal of Neuroimmune Pharmacol. 2012 Jun;7(2):363-71.
Williams K, Hickey WF, Burdo TH and Soulas C. Mononuclear phagocytes. In: The neurology of AIDS. HE Gendelman, I Grant, IP Everall, HS Fox, HA Gelbard, SA Lipton, S Swindells (eds). 2012 Oxford university press.
Zanni MV*, Burdo TH*, Makimura H, Williams KC, Grinspoon S. Relationship between Monocyte/Macrophage Activation Marker Soluble CD163 and Insulin Resistance in Obese and Normal-Weight Subjects. Clinical Endocrinology, accepted October 31, 2011. *Authors contributed equally.
Burdo TH, Lo J, Abbara S, Wei J, Delelys ME, Preffer F, Rosenberg ES, Williams KC, Grinspoon S. Soluble CD163, a Novel Marker of Activated Macrophages, Is Elevated and Associated With Noncalcified Coronary Plaque in HIV-Infected Patients. J Infect Dis. 2011 Oct;204(8):1227-36.
Hou Q, Barr TP, Getsios S, Gee LE, Vickers JV, Rodella LF, Burdo TH, Eisenberg E, Guha U, Wymer JP, McCarthy KC, Kessler JA, Lavker RM, Borsani E, Rice FL, Albrecht PJ, Differential Expression and Modulation of CGRP isoforms in Keratinocytes: Implications for Neuropathic and Inflammatory Pain Mechanisms. Pain. 2011 Sep;152(9):2036-51. Epub 2011 Jun 17.
Strickland S, Gray R, Lamers SL, Burdo TH, Huenink E, Nolan DJ, Nowlin B, Alvarez A, Midkiff CC, Goodenow MM, Williams K, Salemi M. Significant Genetic Heterogeneity of the SIVmac251 Viral Swarm Derived From Different Sources. AIDS Research and Human Retoviruses, Apr 27. [Epub ahead of print].
Burdo TH, Lentz MR, Autissier P, Krishnan A, Halpern E, Letendre S, Rosenberg ES, Ellis RJ and Williams KC. Soluble CD163 made by monocyte/macrophages is a novel marker of HIV activity in early and chronic infection prior to and after anti-retroviral therapy. Journal of Infectious Diseases, Jul;204(1):154-63.
Soulas C, Conerly-Midiff C, Kim W-K, Burdo TH, Alaverz A, Lackner A, Williams KC Recently infiltrating MAC387+ monocyte/macrophages: a third macrophage population involved in SIV and HIV encephalitic lesion formation, American Journal of Pathology, 2011 May;178(5):2121-35. PMID: 21514427.
Campbell JH, Burdo TH, Autissier P, Bombardier JP, Westmoreland SV, Soulas C, González RG, Ratai E-M, Williams KC, Minocycline Inhibition of Monocyte Activation Correlates with Neuronal Protection in SIV NeuroAIDS, PLoS One. 2011 April 6.
Ratai E-M, Pilkenton S, He J, Fell R, Bombardier JP, Joo C-G, Lentz MR, Kim W-K, Burdo TH, Autissier P, Annamalai L, Curran E, O’Neil S, Westmoreland SV, Williams KC, Masliah E, González RG CD8+ Lymphocyte Depletion without SIV Infection does not Produce Metabolic Changes or Pathological Abnormalities in the Rhesus Macaque Brain, J Med Primatol. 2011 Apr 4. doi: 10.1111/j.1600-0684.2011.00475.x. [Epub ahead of print].
Ratai E-M, Annamalai L, Burdo TH, Joo CG, Bombardier JP, Fell R, Hakimelahi R, He J, Lentz MR, Campbell J, Curran E, Halpern EF, Masliah E, Westmoreland SV, Williams KC, González RG, Brain creatine elevation and N-acetylaspartate reduction indicates neuronal dysfunction in the setting of enhanced glial energy metabolism in a macaque model of NeuroAIDS. Magn Reson Med. 2011 Mar 4. doi: 10.1002/mrm.22821. [Epub ahead of print]
2010. Increased monocyte turnover from bone marrow correlates with severity of SIV encephalitis and CD163 levels in plasma. PLoS Pathogens 6(4): e1000842.
Williams, K.C., and Burdo, T.H. 2009. HIV and SIV infection: the role of cellular restriction and immune responses in viral replication and pathogenesis. APMIS 117(5-6): 400–412.
Coutinho, A., Flynn, C., Burdo, T.H., Mervis, R.F., and Fox, H.S. 2008. Chronic methamphetamine induces structural changes in frontal cortex neurons and upregulates frontal lobe type I interferon. Journal of Neuroimmune Pharmacology 3(4): 241–245.
Marcondes, M.C.G., Sopper, S., Burdo, T.H., Sauermann, U., Watry, D.D., Zandonatti, M., and Fox, H. S. 2008. CD4 deficits and disease course acceleration can be driven by a collapse of the CD8 response in SIV-infected rhesus macaques. AIDS 22(12): 1441–52.
Burdo, T.H., Ellis, R., and Fox, H. S. 2008. Osteopontin is increased in HIV-associated dementia. The Journal of Infectious Diseases 198(5): 715–722.
Marcondes, M.C.G., Lanigan, C.M.S., Burdo, T.H., Watry, D.D., and Fox, H. S. 2008. Increased expression of monocytes CD44v6 correlates with the development of encephalitis in rhesus macaques infected with simian immunodeficiency virus. The Journal of Infectious Diseases 197(11): 1567–1576.
Burdo, T.H., Wood, M.R., and Fox, H. S. 2007. Osteopontin prevents monocyte recirculation and apoptosis. The Journal of Leukocyte Biology 81(6): 1504–1511.
Marcondes, M.C., Burdo, T.H., Sopper, S., Huitron-Resendiz, S., Lanigan C., Watry, D., Flynn, C., Zandonatti, M., and Fox, H.S. 2007. Enrichment and persistence of virus-specific CTL in the brain of simian immunodeficiency virus-infected monkeys is associated with a unique cytokine environment. The Journal of Immunology 17(9): 5812–5819.
Burdo, T.H., Katner, S.N., Taffe, M.A., and Fox, H. S. 2006. Neuroimmunity, drugs of abuse and neuroAIDS. Journal of Neuroimmune Pharmacology 1 (1): 41–49.
Burdo, T.H., Marcondes, M.C.G., Lanigan, C.M.S., Penedo, M.C.T., and Fox, H. S. 2005. Susceptibility of Chinese rhesus monkeys to SIV infection. AIDS 19 (15): 1704–1706.
Gaskill, P. J., Watry, D. D. , Burdo, T. H., and Fox, H. S. 2005. Development and characterization of positively selected brain-adapted SIV. Virology Journal 2 (1): 44.
Burdo, T. H., Nonnemacher, M., Irish, B. P., Choi, C. H., Krebs, F. C., Gartner, S., and Wigdahl, B. 2004. High affinity interaction between HIV-1 Vpr and specific sequences that span the C/EBP and adjacent NF-kB sites within the HIV-1 LTR correlates with HIV-1-associated dementia. DNA and Cell Biology 23 (4): 261–269.
Burdo, T. H., Gartner, S., Mauger, D., and Wigdahl, B. 2004. Region-specific distribution of HIV-1 LTRs containing specific configurations of C/EBP site II in brains derived from demented and non-demented patients. Journal of NeuroVirology 10 (1): 7–14.
Quiterio, S., Grant, C., Hogan, T. H., and Wigdahl, B. 2003. C/EBP- and Tat-mediated activation of the HIV-1 LTR in CD34+ hematopoietic progenitor cells. Biomedicine and Pharmacotherapy 57(1): 52–59.
Hogan, T. H., Nonnemacher, M. R., Krebs, F. C., Henderson, A., and Wigdahl, B. 2003. HIV-1 Vpr binding to HIV-1 LTR C/EBP cis-acting elements and adjacent regions is sequence-specific. Biomedicine and Pharmacotherapy 57 (1): 44–51.
Nonnemacher, M. R., Hogan, T. H., Quiterio, S., Wigdahl, B., Henderson, A., and Krebs, F. C. 2003. Identification and characterization of C/EBP cis-acting elements in the simian immunodeficiency virus long terminal repeat. Biomedicine and Pharmacotherapy 57(1): 36–43.
Hogan, T. H., Stauff, D. L., Krebs, F. C., Gartner, S., Quiterio, S., and Wigdahl, B. 2003. Structural and functional evolution of HIV-1 LTR C/EBP sites and their use as molecular markers for CNS disease progression. Journal of NeuroVirology 9 (1): 55–68.
Hogan, T. H., Krebs, F. C., and Wigdahl, B. 2002. Regulation of HIV-1 gene expression and pathogenesis by CCAAT/enhancer binding proteins (C/EBP) in cells of the monocytic lineage. Journal of NeuroVirology 8 (2): 21–26.
Krebs, F. C., Hogan, T. H., Quiterio, S., Gartner, S., and Wigdahl, B. 2002. Lentiviral LTR-directed expression, sequence variation, and disease pathogenesis. HIV Sequence Compendium, 2001. Kuiken, C.L., Foley, B., Hahn, B., Korber, B., McCutchan, F., Marx, P.A., Mellors, J.W., Sodroski, J., and Wolinksy, S., Eds. Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM, 10: 1–42.
Ross, H. L., Nonnemacher, M. R., Hogan, T., Quiterio, S. J., Henderson, A., Krebs, F., and Wigdahl, B. 2001. Interaction between CAAT enhancer binding protein and cyclic AMP response element binding protein 1 regulates human immunodeficiency virus type 1 transcription in cells of the monocyte/macrophage lineage. Journal of Virology 75: 1842–1856.
McAllister, J. J., Philips, D., Millhouse, S., Conner, J., Hogan, T., Ross, H. L., and Wigdahl, B. 2000. Analysis of the HIV-1 LTR NF-kB-proximal Sp site III: Evidence for cell type-specific gene regulation and viral replication. Virology 274: 262–277.
Doern, G.V., Brueggemann, A., Pierce, G., Hogan, T., Holley Jr., H.P., and Rauch, A. 1996. Prevalence of antimicrobial resistance among 723 outpatient clinical isolates of Moraxella catarrhalis in the United States in 1994-1995: results of a 30-center national surveillance study. Antimicrobial Agents and Chemotherapy 40: 2884–2886.