Michael Karin

Bio: Michael Karin is an academic researcher from University of California, San Diego. The author has contributed to research in topics: IκB kinase & Signal transduction. The author has an hindex of 236, co-authored 704 publications receiving 226485 citations. Previous affiliations of Michael Karin include Sanford-Burnham Institute for Medical Research & University of California, Los Angeles.

Compositions and methods for the suppression of mammary epithelial cell proliferation

Abstract: The present invention provides compositions and methods for the suppression of mammary epithelial cell proliferation. In particular, the present invention provides compositions and methods for IKKα kinase inhibition in breast cancer therapy that is relatively free of toxic side effects.

Compositions and methods for detecting and treating cancer

Abstract: The invention provides methods for detecting the presence of cancer initiating cells in a tissue, methods for identifying test agent for reducing cancer, and methods for reducing cancer in a subject. The invention's methods are applicable to any cancer, and in particular to liver cancer. The invention also provides the isolation and characterization of pre-malignant hepatocellular carcinoma initiating cells (HICs). The invention further provides methods for isolating hepatocellular carcinoma initiating cells (HICs), methods for using the isolated cells for screening anti-cancer drugs, methods for using HIC markers for the early diagnosis of hepatocellular carcinoma, and methods for the prevention and/or delay of hepatocellular carcinoma by using agents that selectively deplete the number and/or malignant properties of HICs.

SARS-CoV-2 Seroprevalence Across a Diverse Cohort of Healthcare Workers

Abstract: Importance Antibody testing is important for understanding patterns of exposure and potential immunity to SARS-CoV-2. Prior data on seroprevalence have been subject to variations in selection of individuals and nature as well as timing of testing in relation to exposures. Objective We sought to determine the extent of SARS-CoV-2 seroprevalance and the factors associated with seroprevelance across a diverse cohort of healthcare workers. Design Observational cohort study of healthcare workers, including SARS-CoV-2 serology testing and participant questionaires. Participants A diverse and unselected population of adults (n=6,062) employed in a multi-site healthcare delivery system located in Los Angeles County, including individuals with direct patient contact and others with non-patient-oriented work functions. Exposure Exposure and infection with the SARS-CoV-2 virus, as determined by seropositivity. Main Outcomes Using Bayesian and multi-variate analyses, we estimated seroprevalence and factors associated with seropositivity and antibody titers, including pre-existing demographic and clinical characteristics; potential Covid-19 illness related exposures; and, symptoms consistent with Covid-19 infection. Results We observed a seroprevalence rate of 4.1%, with anosmia as the most prominently associated self-reported symptom in addition to fever, dry cough, anorexia, and myalgias. After adjusting for potential confounders, pre-existing medical conditions were not associated with antibody positivity. However, seroprevalence was associated with younger age, Hispanic ethnicity, and African-American race, as well as presence of either a personal or household member having a prior diagnosis of Covid-19. Importantly, African American race and Hispanic ethnicity were associated with antibody positivity even after adjusting for personal Covid-19 diagnosis status, suggesting the contribution of unmeasured structural or societally factors. Notably, number of people, or children, in the home was not associated with antibody positivity. Conclusion and Relevance The demographic factors associated with SARS-CoV-2 seroprevalence among our healthcare workers underscore the importance of exposure sources beyond the workplace. The size and diversity of our study population, combined with robust survey and modeling techniques, provide a vibrant picture of the demographic factors, exposures, and symptoms that can identify individuals with susceptibility as well as potential to mount an immune response to Covid-19. Key Points Question What is the SARS-CoV-2 IgG seroprevalence rate across a large and diverse healthcare worker population, and which clinical, envionrmental, and symptom-based measures are associated with seropositivity? Findings We observed a seroprevalence rate of 4.1%. Adjusting for potential confounders, seropositivity was associated with younger age, Hispanic ethnicity, African-American race, and the symptom of anosmia, while not significantly associated with any pre-existing medical conditions. Meaning Factors associated with SARS-CoV-2 seroprevalence among our healthcare workers underscore the importance of exposure sources beyond the workplace.

Analysis of NF-κB activation in mouse intestinal epithelial cells.

Abstract: Nuclear factor kappa B (NF-κB) is a key transcription factor controlling inflammation, innate immunity, and tissue integrity NF-κB is activated by IκB kinase (IKK) in response to pro-inflammatory stimuli but is also found to be chronically activated in many inflammatory diseases accompanied by tissue destruction To study the effects of chronic NF-κB activation in intestinal epithelium, we generated IKKβ(EE)(IEC) transgenic mice which express constitutively active form of IKKβ in their intestinal epithelial cells (IEC) In this chapter, we describe three different methods that we applied for analysis of NF-κB activation in IEC of IKKβ(EE)(IEC) transgenic mice: immunohistochemistry (IHC), nuclear fractionation, and chromatin immunoprecipitation (ChIP) These methods can be also applied to analyze NF-κB activation in mouse intestinal tissue in general

Apoptotic cell death in disease—Current understanding of the NCCD 2023

Abstract: Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions. Here, the Nomenclature Committee on Cell Death (NCCD) gathered to critically summarize an abundant pre-clinical literature mechanistically linking the core apoptotic apparatus to organismal homeostasis in the context of disease.

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。

REACTIVE OXYGEN SPECIES: Metabolism, Oxidative Stress, and Signal Transduction

Abstract: Several reactive oxygen species (ROS) are continuously produced in plants as byproducts of aerobic metabolism. Depending on the nature of the ROS species, some are highly toxic and rapidly detoxified by various cellular enzymatic and nonenzymatic mechanisms. Whereas plants are surfeited with mechanisms to combat increased ROS levels during abiotic stress conditions, in other circumstances plants appear to purposefully generate ROS as signaling molecules to control various processes including pathogen defense, programmed cell death, and stomatal behavior. This review describes the mechanisms of ROS generation and removal in plants during development and under biotic and abiotic stress conditions. New insights into the complexity and roles that ROS play in plants have come from genetic analyses of ROS detoxifying and signaling mutants. Considering recent ROS-induced genome-wide expression analyses, the possible functions and mechanisms for ROS sensing and signaling in plants are compared with those in animals and yeast.