Robert J. Lefkowitz

Bio: Robert J. Lefkowitz is an academic researcher from Howard Hughes Medical Institute. The author has contributed to research in topics: Receptor & G protein-coupled receptor. The author has an hindex of 214, co-authored 860 publications receiving 147995 citations. Previous affiliations of Robert J. Lefkowitz include University of Nice Sophia Antipolis & University of Stuttgart.

Inspiring the next generation of physician-scientists

Abstract: As academic physician-scientists, one of the most important things we do is mentor young trainee-scientists. There obviously is no one right way to mentor or a set of rules one can follow; it’s a very personal matter, and very much depends on one’s personality. For much of my career, I gave very little thought as to how I mentored my trainees or to whether I was any good at it. Like many investigators, perhaps, I was just too busy with the daily activities of research to consider how I was guiding my students. Here, I take a look back and reflect on my experiences as a mentor and the factors that I believe contribute to the success of trainees as independent scientists.

Summary of wenner-gren international symposium receptor-receptor interactions among heptaspanning membrane receptors: From structure to function

Abstract: Listening to the talks delivered at the symposium during this 2 1/2-d meeting left me with the feeling that this was a field that has truly come of age in the past few years. Although the earliest observations, a number of them by the organizers of the meeting, on receptor-receptor interactions go back almost two decades, it is really only in the past few years that the molecular basis of these interactions has begun to be clarified. The initial skepticism is now subsiding as more and more examples of receptor oligomerization are identified. At the meeting, three types of receptor oligomerization were discussed: homo-oligomerization; hetero-oligomerization, where both partners are seven transmembrane (7TM)-spanning receptors; and hetero-oligomerization, where a 7 TM-spanning receptor is complexed with a structurally different class of molecule. Although interesting papers were presented in each area, I found myself most intrigued by the papers dealing with hetero-oligomerization between different 7TM-spanning receptors. Most striking were examples where novel functions were created by the heterodimerization process, such as novel opioid binding patterns or the acquisition of novel signaling pathways, as in the case of D1-D2 dopamine receptor heterodimerization. In this connection, to me, one of the most interesting discussions concerned the possibility that a number of currently so-called orphan receptors might have no personal ligands but, rather, function to bestow novel properties on other 7TM-spanning receptors by oligomer formation. Thus, these orphans might convey a new signaling function or an altered ligand- binding specificity on a known receptor. If this were the case then, for such an orphan, all efforts to identify its function by expressing it alone would be doomed to fail. Another potentially interesting function of some orphan receptors might be to act as chaperones for other receptors, helping to bring them to the cell surface and stabilizing their membrane expression.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans

Abstract: Experimental introduction of RNA into cells can be used in certain biological systems to interfere with the function of an endogenous gene Such effects have been proposed to result from a simple antisense mechanism that depends on hybridization between the injected RNA and endogenous messenger RNA transcripts RNA interference has been used in the nematode Caenorhabditis elegans to manipulate gene expression Here we investigate the requirements for structure and delivery of the interfering RNA To our surprise, we found that double-stranded RNA was substantially more effective at producing interference than was either strand individually After injection into adult animals, purified single strands had at most a modest effect, whereas double-stranded mixtures caused potent and specific interference The effects of this interference were evident in both the injected animals and their progeny Only a few molecules of injected double-stranded RNA were required per affected cell, arguing against stochiometric interference with endogenous mRNA and suggesting that there could be a catalytic or amplification component in the interference process

How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions.

Abstract: The secretion of glucocorticoids (GCs) is a classic endocrine response to stress. Despite that, it remains controversial as to what purpose GCs serve at such times. One view, stretching back to the time of Hans Selye, posits that GCs help mediate the ongoing or pending stress response, either via basal levels of GCs permitting other facets of the stress response to emerge efficaciously, and/or by stress levels of GCs actively stimulating the stress response. In contrast, a revisionist viewpoint posits that GCs suppress the stress response, preventing it from being pathologically overactivated. In this review, we consider recent findings regarding GC action and, based on them, generate criteria for determining whether a particular GC action permits, stimulates, or suppresses an ongoing stressresponse or, as an additional category, is preparative for a subsequent stressor. We apply these GC actions to the realms of cardiovascular function, fluid volume and hemorrhage, immunity and inflammation, metabolism, neurobiology, and reproductive physiology. We find that GC actions fall into markedly different categories, depending on the physiological endpoint in question, with evidence for mediating effects in some cases, and suppressive or preparative in others. We then attempt to assimilate these heterogeneous GC actions into a physiological whole. (Endocrine Reviews 21: 55‐ 89, 2000)