Biological & Innovative Researchers

Xianlin Han, PhD

Laboratory studies the role of lipid metabolism in age-related diseases with a major focus on Alzheimer’s disease. Previous work has revealed that among the earliest Alzheimer’s-related lipid alterations is a dramatic deficiency in a class of myelin-specific lipids, known as sulfatide, that is modulated in an age- and apolipoprotein E (apoE) isoform-dependent fashion. Research findings strongly support the notion that sulfatide plays a critical role in apoE-mediated Ab metabolism and Alzheimer’s pathogenesis. Current research efforts focus on elucidating the underlying molecular mechanism(s) leading to sulfatide deficiency at the earliest stages of Alzheimer’s, identifying and describing the consequences of severe sulfatide losses (e.g., Ab deposition, tau hyperphosphorylation, astrocyte activation and ventricular enlargement) and the mechanisms leading to these sequelae and determining the connections between sulfatide deficiency and other Alzheimer’s risk factors (including aging and diabetes). Numerous animal models (e.g., sulfatide conditional knockout mice, AD mouse models, human apoE knockin mice and diabetic animal models) are used to study the role of sulfatide in aging and Alzheimer’s development.

Bess Frost, PhD

The research focus of Dr. Frost’s laboratory revolves around the basic neurobiology connecting toxic forms of tau to neuronal death and dysfunction. Dr. Frost’s contributions to neurodegenerative disease research have recently earned her an O’Donnell Award in Medicine from The Academy of Medicine, Engineering and Science of Texas as well as a Standout Achievement Award from CurePSP. The Frost laboratory has discovered that the detrimental effects of pathogenic tau on nuclear and genomic architecture activate retrotransposons and alter RNA trafficking. Through this work, they have identified multiple new targets for therapeutic development, as well as compounds that interfere with these processes and suppress tau-induced neurotoxicity. Based on these findings, Dr. Frost and her team have recently initiated a Phase IIa clinical trial, ART-AD, in which they are testing the brain penetrance, target engagement, and effects on neurodegeneration and inflammation of the reverse transcriptase inhibitor 3TC in patients with early Alzheimer’s disease.

In addition to her scientific efforts, Dr. Frost is a member of the Tau Consortium and serves on the scientific advisory board of CurePSP. Dr. Frost leads the UT Health Aging Brain Working Group, which aims to bridge the gap between basic science and clinical research.

Peter T. Fox, MD

Bernard Fongang, PhD

Research focuses on developing new computational tools to understand the genetics, genomics and environmental factors driving Alzheimer’s diseases and related disorders. Recent studies have highlighted the association between the gut microbiome, the production of the neurotransmitter serotonin and several neurological disorders. But at the molecular level, how the gut microbiota interacts with the host to produce serotonin and the mechanisms leading to neurological disorders are still not well understood. Research interests include the relationship between serotonin receptors (structurally and functionally), the gut microbiome, the Omics (Genomics, Genetics, Proteomics, Metabolomics) and the risk of dementia, stroke and related neurological endophenotypes. Dr. Fongang’s lab is currently: (i) studying how changes in the gut microbiota are associated with risk of dementia, vascular dementia, and stroke within the Framingham Heart Study; (ii) identifying new genetic loci associated with all-cause dementia and vascular dementia within the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium; (iii) studying the  gene expression patterns and regulatory elements associated with cerebral small vessel disease and vascular dementia; (iv) predicting novel druggable interfaces of serotonin receptors involved in Alzheimer’s disease and related disorders.

These projects involve using and developing cutting-edge algorithms and software to individually study the contribution of each factor (Omics, serotonin receptors, gut microbiome) to neurological disorders and integrate the resulting information to identify profiles associated with risk of cognitive impairment, stroke and dementia with the ultimate goal of personalized medicine.