Richard A Stein

Princeton University, Princeton, NJ, United States

Are you Richard A Stein?

Claim your profile

Publications (6)55.14 Total impact

  • Source
    Casey A Ydenberg, Richard A Stein, Mark D Rose
    [Show abstract] [Hide abstract]
    ABSTRACT: Cell fusion is the key event of fertilization that gives rise to the diploid zygote and is a nearly universal aspect of eukaryotic biology. In the yeast Saccharomyces cerevisiae, several mutants have been identified that are defective for cell fusion, and yet the molecular mechanism of this process remains obscure. One obstacle has been that genetic screens have mainly focused on mating-specific factors, whereas the process likely involves housekeeping proteins as well. Here we implicate Cdc42p, an essential protein with roles in multiple aspects of morphogenesis, as a core component of the yeast cell fusion pathway. We identify a point mutant in the Rho-insert domain of CDC42, called cdc42-138, which is specifically defective in cell fusion. The cell fusion defect is not a secondary consequence of ineffective signaling or polarization. Genetic and morphological data show that Cdc42p acts at a late stage in cell fusion in concert with a key cell fusion regulator, Fus2p, which contains a Dbl-homology domain. We find that Fus2p binds specifically with activated Cdc42p, and binding is blocked by the cdc42-138 mutation. Thus, in addition to signaling and morphogenetic roles in mating, Cdc42p plays a role late in cell fusion via activation of Fus2p.
    Molecular biology of the cell 02/2012; 23(7):1208-18. · 5.98 Impact Factor
  • Richard A. Stein
    [Show abstract] [Hide abstract]
    ABSTRACT: Genetics has fascinated societies since ancient times, and references to traits or behaviors that appear to be shared or different among related individuals have permeated legends, literature, and popular culture. Biomedical advances from the past century, and particularly the discovery of the DNA double helix, the increasing numbers of links that were established between mutations and medical conditions or phenotypes, and technological advances that facilitated the sequencing of the human genome, catalyzed the development of genetic testing. Genetic tests were initially performed in health care facilities, interpreted by health care providers, and included the availability of counseling. Recent years have seen an increased availability of genetic tests that are offered by companies directly to consumers, a phenomenon that became known as direct-to-consumer genetic testing. Tests offered in this setting range from the ones that are also provided in health care establishments to tests known as 'recreational genomics,' and consumers directly receive the test results. In addition, testing in this context often does not involve the availability of counseling and, when this is provided, it frequently occurs on-line or over the phone. As a field situated at the interface between biotechnology, biomedical research, and social sciences, direct-to-consumer genetic testing opens multiple challenges that can be appropriately addressed only by developing a complex, inter-disciplinary framework.
    Journal of Information Technology Research. 01/2012; 5(1):35-67.
  • Richard A Stein
    [Show abstract] [Hide abstract]
    ABSTRACT: It is becoming increasingly apparent that genetic factors are inadequate to fully explain many processes that shape development and disease. For example, monozygotic twin pairs, despite sharing identical DNA sequences, are often discordant for many traits and diseases, indicating that the same genotype can give rise to distinct phenotypes. This points towards the involvement of additional factors that cannot be explained solely by the sequence of the genome. Epigenetic modifications, defined as heritable changes that do not alter the nucleotide sequence, emerge as key factors that regulate chromatin structure and gene expression and, together with genetic factors, provide the mechanistic basis to understand the biological effects of various classes of environmental exposures. Epigenetic mechanisms explain the ability of certain chemical compounds to initiate biological perturbations that can lead to malignancy, despite being weak mutagens or lacking mutagenic activity altogether-a view that challenges old beliefs and opens new avenues in public health. The field of epigenetics also explains the causal link between certain infectious diseases and cancer, a relationship that was first observed over a century ago and was initially discounted, then fell into oblivion and more recently re-emerged as an important concept in biology. A key feature that distinguishes epigenetic modifications from genetic changes is their reversible nature. This provides exciting prophylactic and therapeutic perspectives, some of which already materialised with the approval of the first drugs that modulate the epigenetic machinery, reinforcing the idea that our genes are not our destiny.
    Journal of epidemiology and community health 11/2011; 66(1):8-13. · 3.04 Impact Factor
  • Richard A Stein
    [Show abstract] [Hide abstract]
    ABSTRACT: Early studies that explored host-pathogen interactions assumed that infected individuals within a population have equal chances of transmitting the infection to others. Subsequently, in what became known as the 20/80 rule, a small percentage of individuals within any population was observed to control most transmission events. This empirical rule was shown to govern inter-individual transmission dynamics for many pathogens in several species, and individuals who infect disproportionately more secondary contacts, as compared to most others, became known as super-spreaders. Studies conducted in the wake of the severe acute respiratory syndrome (SARS) pandemic revealed that, in the absence of super-spreading events, most individuals infect few, if any, secondary contacts. The analysis of SARS transmission, and reports from other outbreaks, unveil a complex scenario in which super-spreading events are shaped by multiple factors, including co-infection with another pathogen, immune suppression, changes in airflow dynamics, delayed hospital admission, misdiagnosis, and inter-hospital transfers. Predicting and identifying super-spreaders open significant medical and public health challenges, and represent important facets of infectious disease management and pandemic preparedness plans.
    International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 08/2011; 15(8):e510-3. · 2.17 Impact Factor
  • Richard A Stein
    JAMA The Journal of the American Medical Association 04/2011; 305(14):1484-5. · 29.98 Impact Factor
  • Source
    Richard A Stein
    [Show abstract] [Hide abstract]
    ABSTRACT: A new H1N1 triple-reassortant "swine" influenza virus was recently described in individuals from the United States and Mexico who presented with respiratory symptoms, and the same virus was subsequently confirmed in patients from several countries around the world. The circumstances surrounding the emergence of this pathogen, and the factors that facilitated the initial cross-species transmission, are still incompletely understood. It became apparent in the early days of the outbreak that the virus can be directly transmitted between humans. Pathogens that originate in animal reservoirs and subsequently acquire the potential for human-to-human transmission have caused outbreaks throughout human history. Although each outbreak is marked by its own particularities, it is important to remember the teachings that emerge from previous epidemics and pandemics. Integrating the important lessons of the past will provide the best opportunity to understand host-pathogen interaction and the most powerful approach to implementing effective prophylactic and therapeutic measures.
    Annals of internal medicine 06/2009; 151(1):59-62. · 13.98 Impact Factor