ABSTRACT
PROBLEM: By 2055, the United States will no longer have a single race or ethnic majority. As the nation's demographics change, the field of medicine must also change to meet the needs of diverse patients. APPROACH: In 2013, UT Southwestern Medical Center implemented the Housestaff Emerging Academy of Leaders (HEAL) program, which provides leadership development skills and training to underrepresented in medicine physician residents in preparation for academic medicine careers. Program leaders hypothesized that by providing housestaff with structured mentorship, career coaching, and individualized development plans, HEAL would increase interest in pursuing academic careers and prepare residents for faculty positions. HEAL has since expanded to graduate medical education programs nationwide. OUTCOMES: From 2013 to 2018, HEAL included housestaff at UT Southwestern and other Texas medical centers, totaling 392 enrollees. In 2019, the program increased to include housestaff from around the country. The first HEAL USA program had 39 housestaff, which increased to 173 in 2019, including 60 faculty from 31 U.S. academic medical centers. The 2019 HEAL USA preassessment survey (32 trainee responses) revealed that 10 (31%) of the housestaff were "extremely interested" in academic medicine, but only 1 (3%) felt "extremely confident" to pursue an academic medicine career. Postassessment responses to these same items (5 trainee responses) were 3 (60%) and 1 (20%), respectively, with 3 (60%) also feeling "extremely prepared" (1 [20%]) or "very prepared" (2 [40%]) to pursue an academic medicine career. Of 70 evaluable participants who attended at least 2 sessions and have graduated from residency, 47 (67%) have attained academic faculty positions, whereas 23 (33%) have pursued positions at nonacademic centers. NEXT STEPS: The next steps for HEAL USA will be continued expansion to additional medical centers and effective delivery of career development and leadership training to encourage participants to pursue academic medical careers.
Subject(s)
Academic Medical Centers , Cultural Diversity , Internship and Residency , Leadership , Humans , Internship and Residency/organization & administration , Academic Medical Centers/organization & administration , Female , Faculty, Medical , Education, Medical, Graduate/organization & administration , Male , United States , Texas , Adult , Career Choice , Mentors , Program DevelopmentABSTRACT
Understanding the functional and mechanistic properties of the multi-substrate herpes simplex virus type-1 thymidine kinase (HSV-1 TK) remains critical to defining its role as a major pharmacological target in herpesvirus and gene therapies for cancer. An inherent limitation of the activity of HSV-TK is the >70-fold difference in the K(m)s for phosphorylation of thymidine over the pro-drug ganciclovir (GCV). To engineer an HSV-1 TK isoform that is specific for GCV as the preferred substrate, 16 site-specific mutants were generated. The mutations were concentrated at conserved residues involved in nucleoside base binding, Gln125 and near sites 3 and 4 involved in catalysis and substrate binding. The substrate preferences of each mutant enzyme were compared with wild-type HSV-1 TK. One mutant, termed Q7530 TK, had a lower K(m) for GCV than thymidine. Expression of the Q7530 TK in tumor cells indicated comparable metabolism to and improved sensitivity to GCV over wild-type HSV-1 TK, with minimal thymidine phosphorylation activity. A molecular modeling simulation of the different HSV-1 TK active-sites was done for GCV and thymidine binding. It was concluded that mutations at Gln125 and near site 4, especially at Ala168, were responsible for loss of deoxypyrimidine substrate binding.
