PCMM News

Viet Le, PhD, an instructor in the Springer Laboratory, has been awarded an NIH R03 grant from the National Institute of Diabetes and Digestive and Kidney Diseases. Renal fibrosis is a pivotal factor in the progression of acute kidney injury to chronic kidney disease and ultimately end-stage kidney disease. Transforming growth factor β2 (TGF-β2) is an emerging mediator of renal fibrosis and therapeutic target. Viet’s research focuses on understanding how integrin ααVβ6 activates the latent form of TGF-β2. His R03 project will use super-resolution microscopy to map upregulation of proTGF-β2 and integrin ααVβ6 as well as TGF-β2 activation in the renal fibrotic niche and inves-tigate whether abolishing ααVβ6β6-mediated TGF-β2 activation in vivo attenuates renal fibrosis using a newly developed mouse model. The overall goal of the project is to validate ααVβ6β6-mediated TGF-β2 activation as a therapeutic target for preventing kidney fibrosis.

Quentin Smith, PhD (Ha & Farnung Laboratories) has been awarded an EMBO Postdoctoral Research Fellowship. Faithful cell division and proliferation depend on the careful coordination of essential molecular processes including transcription, DNA replication and repair. Although each process is vital, collisions between their molecular machines can threaten genome stability. Factors such as Transcription Termination Factor I act as critical roadblocks that help prevent these conflicts. As an EMBO Fellow, Quentin will develop biochemical, single-molecule, and structural approaches to characterize these interactions across scales. This work will advance our understanding of how essential chromatin-based processes are coordinated throughout the cell cycle.

Xiaotian Bi, PhD (Ha Laboratory) has been awarded a fellowship through the Protecting the Talent Pipeline in Neurodegeneration Program at BCH. Xiaotian is investigating the molecular mechanisms that drive CAG repeat instability in Huntington’s disease (HD). Somatic expansion of the CAG repeat in the HTT gene is thought to contribute to disease progression, and DNA mismatch repair (MMR) proteins have emerged as key drivers of this process. However, how CAG repeat-containing DNA structures are recog-nized and processed to produce expansion or contraction remains poorly understood. Xiaotian’s work uses single-molecule FRET to visualize the dynamics of CAG repeat DNA structures and their interactions with MMR proteins. She is also developing a sequencing-based MMR-seq platform in mammalian cells to connect defined slip-out DNA structures with cellular repair outcomes. By integrating single-molecule mechanistic measurements with sequencing-based outcome readouts, this work will help reveal the molecular events that bias repeat DNA toward expansion or contraction and provide a mechanistic framework for evaluating therapeutic strategies for HD.

Ninghe Sun, PhD (Zhang Laboratory) has been awarded a fellowship through the Protecting the Talent Pipeline in Neurodegeneration Program at BCH. Aging is the greatest risk factor for neurodegener-ative diseases, including Alzheimer’s disease, but how aging increases vulnerability to cognitive decline remains incompletely understood. Ninghe’s research focuses on how age-associated molecular changes contribute to neurodegeneration, with a partic-ular focus on Clusterin (Clu), a secreted protein that regulates amyloid formation in Alzheimer’s disease. The induction of Clu is associated with aging, cellular stress responses, and decreased neuronal protection. By integrating molecular, cellular, and in vivo approaches, his work seeks to reveal the mechanisms linking Clu regulation to aging biology and progression of neuro-degenerative disease, with the goal of identifying new strategies to preserve brain function, cognitive health, and to promote healthy aging.