The Harvard Chan India Research Center is providing seed grant funding to early career researchers from the Harvard T.H. Chan School of Public Health. For the year 2022-23, pioneering research projects led by Dr Manish Kumar and Dr Matthew Shupler have been funded.
‘Identification of histone lactylation in Plasmodium falciparum as an epigenetic marker of disease severity’ by Dr Manish Kumar
Lactic acidosis or lactic acid build up in the bloodstream of human host is a known clinical feature of severe malaria and is associated with mortality. However, it is unclear how the parasite responds to this lactic acid build up. In vitro studies have shown that parasitic proliferation in human red blood cells, conversion to transmissible sexual forms and antigenic variation are altered in response to the environmental lactate levels. In his research, Dr Kumar has identified that parasitic nuclear proteins such as histones are sensitive to lactate levels and can undergo a modification known as histone lactylation, which can potentially alter the gene expression in P. falciparum parasites. Dr Kumar intends to investigate the host lactate levels and its impact on the parasitic histone lactylation status in severe and non-severe malaria infections.
Dr Kumar is a postdoctoral fellow in the Duraisingh laboratory at the 
Harvard T.H. Chan School of Public Health, with experience in investigating epigenetic mechanisms in Plasmodium falciparum. He carried out his PhD work at the Institute of Bioinformatics, Bangalore, India where he learned advanced tandem mass spectrometry techniques to study quantitative proteomics and protein post-translational modifications. At Duraisingh laboratory, he is using his expertise to understand the epigenetic regulation of the malaria parasite through histone modifications.
So far, Dr. Kumar has measured the blood lactate levels in the severe and non-severe malaria samples at Goa Medical College, Goa, India and observed significantly higher levels of lactate in the patients with severe malaria as compared to the patients with non-severe malaria. Parasites from both severe and non-severe cases were then isolated and subsequently processed at Yenepoya University for further quantitative estimation of histone lactylation levels through comparative proteomics. The samples are being analyzed on high resolution mass spectrometer and the outputs of the study will be shared later this year. A successful outcome of the study will establish a link between the host lactate levels and parasitic histone lactylation status. Such interplay between the host metabolic state and the parasite’s epigenetic code may enable the parasite to alter its life cycle in response to the metabolic challenges encountered during the course of human infection.
‘The impact of household air pollution exposure from cooking and nutrition on metabolic syndrome in five periurban communities in India’ by Dr Matthew Shupler
This project will quantify the relationship between fine particulate matter (PM2.5) exposures from household air pollution, nutritional intake and the odds of metabolic syndrome (MetS) across five peri-urban communities in India. While increased physical inactivity and poorer diets are leading to higher rates of MetS in India, air pollution exposure may also be contributing to the estimated 30% prevalence of MetS in the country. To date, most epidemiological studies have examined the impact of outdoor air pollution on MetS in high-income countries. This study will be one of the first to investigate if foods high in antioxidants or specific nutrients may lower the burden of MetS associated with household air pollution exposure from cooking in India.
Dr Matt Shupler is currently a postdoctoral researcher in the
Department of Epidemiology at Harvard Chan School of Public Health. He completed his PhD in Epidemiology at the University of British Columbia in Vancouver. Over the past decade, Dr Shupler has conducted air pollution research in more than a dozen countries across sub-Saharan Africa, Asia and South America. His research is specifically focused on reducing the adverse health and climate impacts of household air pollution from using polluting fuels (e.g. wood, charcoal) for household energy. His work includes characterizing variation in exposures of PM2.5 and other air pollutants and assessing interventions that contribute to increased use of clean cooking fuels. Dr Shupler has previously worked as a Global Health Fellow at the United Nations Foundation, where he focused on training emerging early career researchers from low and middle-income countries on statistical methods relevant to air pollution epidemiology. Dr Shupler has also partnered with the World Health Organization to communicate the health effects of household air pollution exposure to global audiences.