Jackson, Nicholas
Nick is in the Cell and Developmental Biology home area of the MBIDP. He received a B.A. in Biology and Psychology from Framingham State University and an M.S. in Pharmacology & Drug Development from Tufts University. He joined the CMB training program in 2019.
Mentor: Dr. Leanne Jones
The human intestinal epithelium has a high turnover rate, in which mature cells are replenished every 3-5 days. Intestinal stem cells (ISCs) provide the intestinal epithelium with new cells to maintain, protect, and regenerate the tissue. ISCs are a multipotent population of cells that self-renew and replicate to give rise to the diverse population of cells that make up the intestine. The small intestine (SI) has a crypt-villus structure in which the ISCs are located at the crypt base; in contrast, the large intestine (colon) contains only crypts. ISCs are located in the bottom of the crypt and differentiate as they travel up the crypt. The improper function and regulation of ISCs have been associated with intestinal disease such as Inflammatory Bowel Disease (IBD; ulcerative colitis and Crohn’s disease) and cancers of the gut (gastrointestinal stromal tumors and colorectal cancer). Studying the molecular components and functions that contribute to ISC’s can provide insight into the development of these various diseases and highlight potential targets for therapeutic intervention.
I would like to study the L1 cell adhesion molecule (L1CAM), and its role in the intestine. L1CAM is best known for its role in the development of the nervous system by facilitating cell motility, cell adhesion and axonal outgrowth. However, L1CAM has been identified near the crypts in the murine intestine but its function is undetermined. Furthermore, L1CAM expression has been identified in many human cancers, leading to cell migration, metastasis, and decreased survival. While murine studies are a helpful research tool, they are not always an accurate prediction for humans, thus warranting the need for investigation of L1CAM in healthy human intestinal tissue. I hypothesize that L1CAM is expressed in the human intestine and contributes to the proper function of ISCs, and its dysregulation results in intestinal disease.
To address the lack of knowledge of L1CAM, I will use basic molecular biology techniques to provide a better understanding of its role in the human intestine. To do so, we will utilize patient samples provided from the University of California, Los Angeles’ Translational Pathology Core Laboratory (TPCL) to perform immunofluorescence (IF) staining. IF experiments will allow us to identify possible L1CAM expression in the intestine, including its specific location. The patient samples also provide the opportunity to generate intestinal organoids that allow for in vitro studies. The intestinal organoid system is capable of recapitulating the ongoing regenerative properties of the intestine in a dish. Using well-established protocols, the ISC-containing crypts can be easily purified away from whole mucosa and subsequently, the crypts can be used to generate intestinal “spheroids”, which contain ISCs and lack differentiated cells, and “enteroids”, which contain ISCs and differentiated cells.
