Dr. Mallika Ghosh
Center for Vascular Biology
Undergraduate Research Opportunity Description
|Project Description||CD13 is a multifunctional cell surface peptidase that is expressed on a variety of cells where we have shown that it modulates receptor-mediated endocytosis and ligand internalization to control downstream signaling pathways. We will explore how CD13 regulates receptor endocytosis and recycling of two major receptors S1P1 receptor and beta1 Integrin receptor which are involved in fundamental cellular function. We will track the receptor by immunostaining followed by fluorescence microscopy. The two main projects are as follows:
1. CD13 mediated regulation of endocytosis and recycling of G-protein coupled receptor, S1P1 receptor induced by its ligand S1P/FTY-P to regulate cytoskeletal remodeling in vitro and in vivo.
2. Regulation of beta1 Integrin recycling, cell migration and focal adhesion turnover by CD13 in cancer epithelial cells.
|Project Direction||Project # 1- CD13 mediated regulation of endocytosis and recycling of G-protein coupled receptor, S1P1 receptor induced by its ligand S1P/FTY-P to regulate cytoskeletal remodeling in vitro and in vivo
Biologically active sphingolipid, S1P is formed by the phosphorylation of sphingosine by sphingosine kinases and exported outside the cell where it can activate its receptors. The pleiotropic effects of S1P in cells are mostly mediated through its interaction with five G-protein-coupled receptors namely S1P(1-5) receptors.
In this project we will explore the functional role of CD13 in the regulation of S1P1 receptor in actin cytoskeletal changes and downstream signaling. These studies will be performed in in vitro cell culture system and in in vivo mouse model of fibrosis.
Project # 2- Regulation of beta1 Integrin recycling, cell migration and focal adhesion turnover by CD13 in cancer epithelial cells.
During metastasis cells need to invade the extracellular matrix (ECM) that surrounds tissues and tumors, and must survive and grow within these microenvironment. As they invade, tumor cells form dynamic interactions with the ECM that provide force for forward motion and also promote cell growth and survival. Motility, growth and survival of tumor cells are controlled by Integrins.
In this project we will explore the functional role of CD13 as a critical regulator of Integrin receptor recycling regulating fundamental cellular processes namely signal transduction, cell migration, cell adhesion and autophagy. These studies will be performed in cancer epithelial cell lines isolated from both mouse and human.
|Mentorship and Supervision||I will send an outline of the research project and relevant scientific papers one week before the program.
In the first week, I will discuss and explain the entire project and allow the student to read about the project.
During the first few weeks I will teach the student all the laboratory techniques relevant to the project and explain how to record data. Initially, we will start working on the project together. At this time the student will slowly begin to perform experiments under my supervision. Once I am confident that the student can perform experiments independently, I will allow the student to do experiments by himself/herself but under my watchful eye. Everyday, when the student arrives I will briefly discuss the experiment that we planned for that day and the student will write down the day’s work in the laboratory notebook. At the end of the day, the student will enter the data in the laboratory notebook and we will discuss and summarize the day’s work. Every Friday, the student will make a PowerPoint presentation of the data in the lab meeting. At the end of the program, the student will give a PowerPoint presentation of the entire research project in the laboratory. I will provide feedback to the student on a regular basis. I will encourage the student to come up with an explanation and solution if a particular experiment fails and provide words of encouragement if he/she succeeds.
|Student Qualifications||Academic interest related to receptor mediated endocytosis, intracellular trafficking, signal transduction and protein-protein interaction.
Research experience in any of the following areas will be extremely helpful:
|Summer Schedule Options||Research Dates: May 8 – July 7, 2017
Schedule: M-F, 9am-4pm
|Project Continuation||Fall 2017, Spring 2018|
|Academic Year Time Commitment||3-6 hours/week|
|Possible Thesis Project||Yes|
Submit an online application for this research opportunity using the form below. The application deadline is Friday, February 24, 2017.
This application requires a cover letter, a resume or CV, a brief statement of research interests, a brief statement of career interests, and contact information for references.