Howard S. Fox, MD, PhD

Howard Fox

Research
Representative Publications
Biographical Information
Visit Dr. Fox's Lab

HOWARD S. FOX, MD, PhD
Professor

University of Nebraska Medical Center
Durham Research Center 3008
985800 Nebraska Medical Center
Omaha, NE 68198-5800

Phone: 402-559-4820
E-mail: hfox@unmc.edu

Keywords: SIV, HIV, NeuroAIDS, Methamphetamine, CNS Dysfunction


In the News:

Graduate Student Philip Purnell is 2014-2015 University of Nebraska Presidential Graduate Fellow

UNMC Today, April 21, 2014
Meet Scientist Laureate Howard Fox, M.D., Ph.D.

January 10, 2013 -InterCOM, A newsletter from the College of Medicine, UNMC
Research opportunities rampant, but limited funding poses challenge

July 15, 2011  -UNMC Today
Core facility helps Drs. Fox and Sarvetnick secure $3 million NIH grant

March 21, 2011 - UNMC Today
UNMC Grants - $9 million award for study of aging and HIV infection

July 6, 2010 - UNMC Today
Dr. Fox named to key research post for College of Medicine

May 4, 2010 - HIV and Aging Workshop


In his own words - listen to Dr. Fox discuss careers in science and his research.

Research:
The brain is a unique organ, not only functionally but also in terms of host response to events such as damage and infection. We study processes in which this response leads to neurodegeneration and brain dysfunction. Much of our recent work has focused on biomarkers, which are objectively measured markers that correlate with disease states. They are useful for predicting risk of disease, development of disease, response to therapy, and other medical indications. Furthermore, they can give important clues to pathogenic mechanisms leading to means to prevent and treat disease. There is a distinct lack of such biomarkers in neurodegenerative diseases, representing a significant gap in our biomedical knowledge.

Our primary work models the development of neurodegeneration leading to dementia utilizing a brain disease that results after a known stimulus, infection with HIV. Using infection of rhesus monkeys with simian immunodeficiency virus (SIV) as a model of neuroAIDS, we are studying the virology, immunology, pathology, neurobiology, and molecular basis of the resulting central nervous system (CNS) disease. Two recent examples of this work are given below.

First, using “omic” technologies, we have discovered novel biomarkers for CNS disease, leading to mechanistic insights into neurodegenerative processes. Among these is the finding of osteopontin as a marker for HIV induced dementia, as well as the correlation of increased expression of one of its receptors on monocytes, CD44v6, with SIV encephalitis. Mechanistically, we have found that osteopontin acts to increase macrophage accumulation within tissues, paralleling the increased macrophages in the brain that are responsible for HIV dementia.

Second, we have embarked on a novel project assessing whether metabolites in the cerebrospinal fluid (CSF) would be useful as candidate biomarkers. Indeed they are, and using a combination of metabolomic and transcriptomic profiling, we have identified multiple new CSF biomarkers, which led to the discovery of a distinct mechanism of SIV-induced CNS disease. This work is now expanding to encompass other CNS disorders and holds great promise in having significant basic and applied impact.

Students and postdoctoral trainees can participate in a number of the projects in Dr. Fox’s laboratory. Those interested in molecular training can join projects involved in synthesizing the combined transcriptomic, proteomic, and metabolomic data to examine pathophysiological mechanisms of disease. Those with interests in virology, immunology and/or neuroscience can help us probe the immune response to infection within the brain, and assess its effect on neuronal function. While each trainee will have an independent project, the common themes involve several members of the group.

Representative Publications

Gaskill PJ, Zandonatti M, Gilmartin T, Head SR, and Fox HS. (2008). Macrophage derived SIV exhibits enhanced infectivity by comparison with T cell derived virus. Journal of Virology 82: 1615-1621.

Marcondes MC, Lanigan CM, Burdo TH, Watry DD, and Fox HS. (2008). Monocyte CD44v6 Correlates with the Development of Encephalitis in SIV-Infected Rhesus Macaques. Journal of Infectious Diseases 197: 1567-1576.

Marcondes MC, Sopper S, Sauermann S, Burdo TH, Watry DD, Zandonatti MA, and Fox HS. (2008). CD4 deficits and Disease Course Acceleration can be driven by a collapse of the CD8 response in SIV-infected Rhesus Macaques. AIDS 22: 1441-1432.

Wikoff WR, Pendyala G, Siuzdak G, and Fox HS. (2008). Metabolomic analysis of the cerebrospinal fluid reveals changes in phospholipase expression in the CNS of SIV-infected macaques. Journal of Clinical Investigation 118: 2661-2669.

Alirezaei M, Kiosses WB, Flynn CT, Brady NR, and Fox HS. (2008). Disruption of neuronal autophagy by infected microglia results in neurodegeneration. PLoS ONE 3: e2906.

Burdo TH, Ellis RJ, Fox HS. (2008). Osteopontin is increased in HIV-Associated Dementia. Journal of Infectious Diseases 198(5):715-722.

Marcondes MC, Watry DD, Zandonatti MA, Flynn CT, Taffe MA and Fox, HS. (2008). Chronic alcohol consumption generates a vulnerable immune environment during early SIV infection in rhesus macaques. Alcoholism: Clinical and Experimental Research 9:1583-1592.

Coutinho A, Flynn C, Burdo TH, Mervis RF, and Fox HS. (2008). Chronic Methamphetamine Induces Structural Changes in Frontal Cortex Neurons and Upregulates Type I Interferons. J. Neuroimmune Pharmacology 4:241-245.

Marcondes MC, Poling M, Watry DD, Hall D, and Fox HS. (2008). In vivo Osteopontin-induced Macrophage Accumulation is Dependent on CD44 Expression.Cellular Immunology 254(1):56-62.

Marcondes MC, Flynn C, Huitron-Rezendiz S, Watry DD, Zandonatti M, Fox HS. (2009) Early antiretroviral treatment prevents the development of central nervous system abnormalities in simian immunodeficiency virus-infected rhesus monkeys. AIDS 23(10):1187-95.

Gersten M, Alirezaei M, Marcondes MC, Flynn C, Ravasi T, Ideker T, Fox HS. (2009) An integrated systems analysis implicates EGR1 downregulation in simian immunodeficiency virus encephalitis-induced neural dysfunction. J. Neurosci. 29(40): 12467-76.

Marcondes MC, Flynn C, Watry DD, Zandonatti M, Fox HS. (2010) Methamphetamine Increases Brain Viral Load and Activates Natural Killer Cells in Simian Immunodeficiency Virus-Infected Monkeys. Am J Pathol Jul;177(1):355-61.

Purnell PR, Fox HS (2013). Autophagy-mediated turnover of dynamin-related protein 1. BMC Neuroscience, 14: 86. PMCID: PMC3750610.


Villeneuve L, Tiede LM, Morsey B, Fox HS (2013). Quantitative proteomics reveals oxygen-dependent changes in neuronal mitochondria affecting function and sensitivity to rotenone. J Proteome Research, 12: 4599-4606. PMCID: PMC3909963


Chaudhuri AD, Yelamanchili SV and Fox HS (2013). MicroRNA-142 Reduces Monoamine Oxidase A Expression and Activity in Neuronal Cells by Downregulating SIRT1. PLoS ONE, 8: e79579. PMCID: PMC3823651


Yelamanchili SV, Morsey B, Rennard DA, Harrison EB, Emanuel K, Bastola DK, and Fox HS (2014). The evolutionary young miR-1290 favors mitotic exit and differentiation of human neural progenitors through altering the cell cycle proteins. Cell Death and Disease, 5: e982. PMCID: PMC4040694.


Becker KM, Heinrichs-Graham E, Fox HS, Robertson KR, Sandkovsky US, O’Neill J, Swindells S, Wilson TW. Decreased MEG beta oscillations in HIV-infected older adults during the resting-state. J Neurovirology, 19: 586-594. PMCID: PMC3913174


Haverland NA, Fox HS, Ciborowski P. (2014). Quantitative Proteomics by SWATH-MS Reveals Altered Expression of Nucleic Acid Binding and Regulatory Proteins in HIV-1-Infected Macrophages. J Proteome Research, 13: 2109-2119. PMCID: PMC3993959.


Stauch KL, Purnell PR, Fox HS. (2014). Quantitative Proteomics of Synaptic and Nonsynaptic Mitochondria: Insights for Synaptic Mitochondrial Vulnerability. J Proteome Research, Epub ahead of print. PMCID: PMC4105687


Stauch KL, Purnell PR, Fox HS. (2014). Aging synaptic mitochondria exhibit dynamic proteomic changes while
maintaining bioenergetic function. Aging, Epub ahead of print. PMCID: PMC4032798.

 

 

Additional publications listed in PubMed 

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