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David Wasserman

Publications and source records attributed to David Wasserman.

17 recordsLinked to original sources

p38MAPK acts in the BMP7-dependent stimulatory pathway during epithelial cell morphogenesis and is regulated by Smad1.

Bone morphogenetic protein (BMP)-7 exerts dose-dependent stimulatory and inhibitory effects during renal branching morphogenesis. Previously, we identified an inhibitory role for activin-like kinase receptors and Smad1 in BMP-dependent inhibition (Piscione, T. D., Phan, T., and Rosenblum, N. D. (2001) Am. J. Physiol. 280, F19-F33). Here we demonstrate a novel role for p38 mitogen-activated kinase (p38(MAPK)) in BMP7-dependent stimulatory signaling. Stimulatory doses (0.25 nm) of BMP7 increased p38(MAPK) activity and stimulated phosphorylation of endogenous activating transcription factor 2 (ATF2) in a p38(MAPK)-dependent manner in murine inner medullary collecting duct (mIMCD-3) cells. In contrast, high doses (10 nm) of BMP7 inhibited p38(MAPK) activity and phosphorylation of endogenous ATF2. Treatment with BMP7 exerted no significant effect on the levels of the phosphorylated forms of endogenous SAPK/JNK or p44 and p42 (ERK1 and ERK2) protein kinases. To investigate the functional importance of p38(MAPK) signaling, we showed that SB203580, a p38(MAPK) inhibitor, blocked the stimulatory effect of BMP7 on mIMCD-3 cell morphogenesis but had no effect on BMP7-dependent inhibition in a three-dimensional culture model. To identify mechanisms by which BMP7-dependent inhibitory signaling suppresses p38(MAPK) activity, we measured p38(MAPK) activity in ligand independent mIMCD-3 models of enhanced and suppressed Smad signaling. Basal activity of p38(MAPK) was decreased in mIMCD-3 cells and in embryonic kidney tissue expressing a constitutively active activin-like kinase receptor, but was increased in mIMCD-3 cells stably expressing a dominant negative form of Smad1. We conclude that BMP7 stimulates renal epithelial cell morphogenesis via p38(MAPK) and that p38(MAPK) activity is negatively regulated by Smad1.

Activating Transcription Factor 2↗

Addiction and disability: moral and policy issues.

This article discusses the conceptual, ethical, and policy issues raised by the legal classification of drug addiction as an impairment, and of some nonusing drug addicts as people with disabilities. It focuses on the questions of (1) what moral judgments, if any, underlie the classification of addiction as an impairment; (2) whether it makes sense to apportion the burdens of drug addiction between chemical, biological, social, political, and other causes; (3) how considerations of distributive justice may compel or constrain measures to ease the burdens of drug addiction; and (4) whether it is justifiable to deny the current users of illegal substances legal protections available to the current users of legal substances.

Attitude to Health↗

Impact of medical student research in the development of physician-scientists.

CONTEXT: A decline in the number of physician-scientists has been identified in the United States for at least two decades. Although many mechanisms have been proposed to reverse this trend, most of these have concentrated on MD/PhD programs, research in sub-specialty fellowships, and other approaches later in physician training. Few have emphasized early medical student research experiences as a contributing solution. OBJECTIVE: To determine the effect of a medical student research experience on career choices and attitudes about biomedical research. DESIGN, SETTING, AND PARTICIPANTS: We jointly report 25 years of experience with National Institutes of Health (NIH)-sponsored Medical Student Research Fellowship programs (MSRFs) at two colleges of medicine, the University of Tennessee Health Science Center and Vanderbilt University. In both programs, students work during the summer of their first or second year of medical school on a research project that is mentored by an established scientist and participate in a structured program (lectures, visiting professor). MAIN OUTCOME MEASURES: We gathered data using pre- and postresearch fellowship questionnaires to assess (a) quality of research experiences; (b) tabulation of productivity, that is, presentations, abstracts, publications, and awards; (c) long-term tracking of former program participants; (d) comparison of residency placements by medical student researchers; and (e) comments from former program participants on the effects of their students' research experiences on career choices. RESULTS: During this time, approximately 1,000 medical students participated in the two programs. Follow-up data (for short-term evaluations, 96-132 respondents with a response rate > 82%; for long-term evaluations, 88-118 respondents with a response rate > 29-33%) strongly suggest (a) interest in an academic career increased, (b) one-third to half of former student respondents considered themselves to be in academic medicine, (c) the vast majority of students conducted additional research after their medical student research experience, and (d) a large number of students were currently doing research or had published or presented their work at scientific meetings. CONCLUSIONS: Over two decades of experience with NIH-sponsored medical student research programs at two medical schools strongly support the ability of these programs to interest medical students in research and academic careers. MSRFs should be included in strategies to reverse the decline in the number of physician-scientists.

Attitude↗