Research: The research carried out in my lab focuses on understanding the mechanism of function, at the atomic and molecular level, of proteins important for proper midline development during embryogenesis. We showed for the first time that MID1 directly interacts with microtubules and solved the NMR solution structures of a region of MID1, called the COS box, that is critical for microtubule-binding. The first structure of a COS box revealed a new protein fold that can bind to microtubules.
Unlike several mutations that we have shown cause protein unfolding, and hence loss of MID1 function, we recently showed that a proline to leucine at position 151 (P151L) mutation did not significantly affected the overall structure of the B-box1 domain or the E3 ligase. In fact, the P151L mutation lead to an enhancement of MID1 E3 ligase activity. However, MID1 failed to catalyze the ubiquitination of alpha4 and an increase in alpha4, which can protect PP2A might explain the increased in PP2A observed in XLOS-derived embryonic cells.
There are two additional research interests in the lab: MID1 as part of a multiprotein complex is shown to play a role in Huntington’s Disease, although its mechanism of action is not clear. There is no cure of Huntington disease and the most feasible approach for a cure is to prevent the synthesis of the mutant huntingtin (mHTT) protein. This multiprotein complex stabilizes the mRNA of mHTT and facilitate synthesis of the mutant protein. We now have preliminary data that show multiple regions/domains of MID1 bind the mutant region of the mHTT mRNA. To facilitate this aspect of the research, we have embarked on synthesizing and purifying RNA to perform MID1-RNA binding studies. RNA is extremely expansive and not feasible to purchase. We also will design various RNA sequences. By understanding the mechanism of interaction, we can identify sites for therapeutic interventions to disrupt the MID1-RNA interaction and hence prevent mHTT synthesis. The next area of interest is MID1’s role in breast and ovarian cancers. This project involves the structural characterization of a new protein, EDD, that can regulate the E3 ligase activity of MID1. EDD belongs to the other of the two classes of enzymes that facilitate protein ubiquitination and this will allow us to understand how RING and HECT E3 ligases function.
Teaching: I continue to teach students with rigor to prepare them to be highly successful for post-GWU careers. I take teaching seriously and expect the same commitment from students. I constantly look for ways to get students to be engaged and improve without compromising course requirements and expectations. My students view me as challenging but I believe I am no more challenging than any colleagues. I do demand students take personal responsibility in their learning, a dedicated effort and commitment to not just pass the exams or obtain a good grade but to understand, appreciate and extrapolate chemistry as it applies to life and human health. The idea that students must understand the material to do well is challenging to students. These requirements, I believed, causes students some anxiety and to view me negatively.
Service: I continue to be involved in activities that serve in the best interest of and reflect well on the university, college and department. First, I continue to promote research and STEM opportunities for minority high school students in the greater DC/MD/VA area. I served on the board of the ACS Project SEED program, recruiting economically disadvantaged minority students to the program and identifying faculty at GWU who could host students for 6-8 weeks during the summer. I continue to work with Wheaton High School to place minority students in labs at GWU. During the summer of 2018, I placed 4 Project SEED students into labs at GWU, including one in my lab.
I continue to serve as an Associate Editor for PLOS ONE and on two NSF panels.
I peer-reviewed journal articles from ACS Omega, Analytical chemistry, PLOS One, and Nature’s Scientific Report.
Within the university, I have served on the Academic Council of Research for the OVPR, reviewing applications for new and recharter of centers and institutes, reviewing proposals for the UFF and cross-disciplinary Research fund (CDRF).
I served on the search committee for a new CCAS dean (search selected five candidates but eventually failed)
I have also served as judge in the fall and spring semester for the GTAP programs, evaluating GTAP student presentations.
At the college level, I have served on the APR committee to evaluate the Biochemistry department and provided my findings in writing to the dean's office.
I also served on the committee organizing the interdisciplinary WOW Talks to promote collaboration with the SEH.
Service At the department level, I served on a committee that successfully developed the Department's strategic plan and mission. The plan was ratified and approved by the department and will serve as a road map for the next 3-5 years.
I continue to take care of the departmental 400 MHz NMR spectrometer, and I trained all users. I also helped with maintaining the departmental Dynamic Light Scattering (DLS) instrument, now used by groups in Chemistry, physics, biology, and mechanical engineering.
I served on the thesis committees of Kenny Heidel (Dowd's group) and Rinipal Kaur (Sadtchenko’s group). I continue to serve as mentor to Claire Besson and provide guidance to improve her NSF proposal (for which one was funded by the NSF).