Keith Mansfield, DVM

Associate Professor, Department of Pathology

Harvard Medical School

The New England Primate Research Center

Infectious diseases and aging: simian AIDS; opportunistic infection; diet

Infectious diseases, aging, and dietary intervention.

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Commercial Opportunities

Investigate SIV-related disease as well as other infectious diseases, including tuberculosis and influenza; study the effects of diet, inflammation, and insulin resistance in the context of normal aging and aging-related diseases that are vital for designing new diagnostics, preventative treatments, and drugs.

The National Center for Research Resources (part of the NIH) provides a portion of the lab’s funding; its mandate is to “transform basic discoveries into improved human health.” The lab’s robust SIV program is uncovering important modifiers of infectivity and disease progression, such as the pronounced effect of diet, which may lead to new therapies to ameliorate the disease pathology. In addition, the deleterious effects of opportunistic infections, and the concomitant inflammatory responses, are critical issues facing HIV patients. Insights into their etiologies may uncover new molecular targets for combating these infections. Other infectious diseases such as TB and influenza are also being studied under BL3 containment, a valuable capability that allows for validation of models.

The lab is also actively harnessing its expertise in non-human primate development, biology, and pathology, to study aging and age-related illnesses where there is a signficant unmet medical need, and would be interested in collaborating with corporate partners to further enhance these studies. The surge in drug development efforts in this sector is indicative of the large market for new anti-aging treatments. Investigation into factors such as diet, inflammation, and insulin resistance, in the context of normal aging and aging-related diseases, such as Alzheimer’s disease, may be vital for designing new diagnostics, preventative treatments, and drugs. Also, the lab would be interested in partnering with companies that can furnish imaging equipment (for example, PET, MRI) for its on-site use.
 

Current Research Interests
  •  Modeling of various human clinical conditions in non-human primates, including infectious disease, aging, and the relationship of diet to disease.
     
  • Studying the pathogenesis and morbidity of infectious diseases, such as SIV (as a surrogate for studying HIV infection), including vaccines and opportunistic infections.
     
  • Exploring dietary factors, such as fat and cholesterol, that impact the viral process, including infectivity, inflammation, and the overall disease course.
     
  • Studying the biology and therapeutic approaches for other infectious agents requiring BL3 containment, including SARS, TB, measles, and influenza.
     
  • Investigating the effect of diet and body composition on the aging process and age-related diseases, such as Alzheimer’s disease, and assessing links with proinflammatory mediators and insulin resistance.
     
Research Expertise

Dr. Mansfield’s laboratory focuses on infectious diseases, vaccines, aging, and dietary intervention. The laboratory has performed extensive investigations into the pathophysiology of inflammation and infections in non-human primates, with particular emphasis on opportunistic infections accompanying SIV-infection. The immune pathophysiology associated with HIV/SIV retroviral infection is complex and not completely understood, particularly with respect to the associated disorders that afflict organs, such as the heart (for example, myocarditis) and the brain (for example, AIDS dementia complex). The laboratory has examined phenotypic alterations in macrophage subtypes associated with SIV infection as a model of HIV myocarditis in humans. The lab’s morphometric analysis of myocardial tissue revealed immunophenotypic changes in monocytic and lymphocytic populations, suggesting that specific alterations in these cell types may be associated with the presence of the virally-infected cells found in the cardiac environment.

A separate line of inquiry by the lab has explored the role of diet on SIV-related disease. Its findings may have significant clinical relevance, because it has demonstrated that a diet enriched in cholesterol and saturated fatty acids enhances disease progression and produces an elevated risk of death. These compelling data lay the foundation for future studies in humans, where modulation of fat and cholesterol intake may help curb the progression of AIDS in HIV-infected individuals.