Mol Bio Colloquium

Feb 4, 2022, 4:00 pm5:00 pm
Thomas Laboratory, 003 or via Zoom
Free and open to the university community and the public.


Debra Ouyang
Graduate Student
Devenport Lab
Jun Yan
Graduate Student
Adamson Lab
Moamen Elmassry
Postdoctoral Fellow
Donia Lab


Event Description


February 4, 2022




Devenport Lab

Understanding the mechanisms that maintain planar cell polarity during cellular division

The skin epithelium is constantly exposed to environmental and mechanical stresses throughout life. In order to preserve tissue structure and function, epithelial stem cells must continuously divide and differentiate to replenish and replace aged or damaged tissue. Despite the epithelium undergoing constant growth, repair and regeneration, how epithelial stem cells are able to concomitantly maintain cell polarity, an essential architectural feature of all epithelia organs, remains poorly understood. In particular, it is essential for planar cell polarity (PCP) to be preserved during cellular division as loss of polarity can impair tissue architecture and integrity.  
The Devenport Lab has established the murine skin as a powerful model system to investigate the mechanisms of PCP establishment and maintenance in a highly dynamic tissue. We previously identified a novel mechanism for PCP preservation in dividing epidermal stem cells involving the bulk endocytosis of PCP proteins during the onset of mitosis, which results in a temporary loss of PCP that is later restored in daughter cells. With the lab's recent development of mouse lines with endogenously-tagged PCP proteins, it is now possible to investigate the temporal and spatial mechanisms of PCP preservation in greater detail. Novel findings from this study will be informative for how polarity is maintained and restored in a highly dynamic tissue.




Adamson Lab

Understanding the genetics of prime editing with repair-seq and genome-scale CRISPRi screens

Prime editing is a recently developed versatile tool that uses reverse transcription to precisely copy RNA-templated sequence into the genome. But how it works mechanistically, especially how the generated DNA intermediates are resolved by DNA repair machineries, has remained unclear. To address this question, we first employed repair-seq CRISPRi screen platform to systematically identify DNA repair factors that affect the editing outcomes. As a result, we found that DNA mismatch repair (MMR) strongly suppresses prime editing. Moreover, co-delivering a dominant negative MLH1 to inhibit MMR during editing significantly increases the intended editing efficiency and reduces indels. Next, I performed a reporter-based genome-scale CRISPRi screen to obtain more mechanistic insight. With a thorough understanding of prime editing, we aim to improve its efficiency and precision.







Donia Lab

Interrogating the gut microbiome of colorectal cancer patients

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths in the US. Every year, ~150,000 new CRC cases are reported. Several factors can increase the risk for CRC, i.e., genetics, lifestyle, and the gut microbiome. While human genetics and lifestyle have been extensively studied for their role in CRC development, the role of the gut microbiome is still unclear. Therefore, this project aims to interrogate the role of the gut microbiome and its small molecule products in CRC development. First, I will perform a meta-analysis of metagenomic data of CRC cohorts and their matched controls to identify CRC-associated small molecules biosynthetic gene clusters. Then, I will utilize in vitro and in vivo screening assays to prioritize and test the role of specific microbiome members in CRC development. The small molecule products of the prioritized gut microbiome members will be pursued to establish possible causal links. These experiments will highlight the potential role of the gut microbiome in CRC development and will inform future endeavors to target exact microbiome members for developing new therapies.



Department of Molecular Biology
Event Category
Graduate Student Colloquium