Richard Ansel Lockshin

Richard Ansel Lockshin
St. John's University · Department of Biological Sciences

PhD

About

187
Publications
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Introduction
Skills and Expertise

Publications

Publications (187)
Article
In June of 2019, the International Cell Death Society (ICDS) held its 25th anniversary meeting in New York City at the Icahn School of Medicine at Mount Sinai organized by Drs. Richard A. Lockshin (St. John’s University, USA), Zahra Zakeri (Queens College, USA), and Jerry Edward Chipuk (Icahn School of Medicine at Mount Sinai, USA). The three‐day e...
Article
Full-text available
Varicocele, defined as enlarged varicose veins in the scrotum, is the most common identifiable cause of male infertility. There are significant correlations between oxidative stress and varicocele-related infertility due to testicular hyperthermia, which can result in low sperm function. In addition, recent excessive oxidative stress can affect spe...
Article
Influenza virus causes infected cells to generate large numbers of lipid droplets. Because the virus envelope contains substantial cholesterol, we applied atorvastatin (ATV) to Madin-Darby Canine Kidney cells before infecting them. Five micromolars ATV, within physiologic range, strongly (>95%) inhibits reproduction of influenza A as measured by PC...
Article
Full-text available
In chemotherapy, two or more pharmaceuticals targeting different metabolic pathways are often combined in the expectation that they will synergize or function additively against the tumor. Flavonoids, typically polycyclic plant pigments, have many beneficial effects in humans, including being putatively anticancer, inducing apoptosis by undefined m...
Article
Abnormal dilatation and tortuosity of the pampiniform plexus within the spermatic cord are termed varicocele which leads to impaired spermatogenesis due to heat‐related oxidative stress and cell death. Previously, it was shown that both apoptosis and autophagy pathways were activated by heat in germ cells of mouse in vivo and in vitro. But, status...
Article
International Cell Death Society held its 25th meeting, entitled "About canonical, non-canonical, and immunogenic cell death: basic mechanisms and translational applications" in Seoul, South Korea, May 31-June 2, 2018, addressed the most current issues in the field. Now that many types and pathways of cell death are recognized, attention has turned...
Article
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Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated c...
Preprint
Full-text available
Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated c...
Article
Full-text available
A virus that reproduces in a host without killing cells can easily establish a successful infection. Previously, we showed that dengue-2, a virus that threatens 40% of the world, induces autophagy, enabling dengue to reproduce in cells without triggering cell death. Autophagy further protects the virus-laden cells from further insults. In this stud...
Article
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In the 50 years since we described cell death as 'programmed,' we have come far, thanks to the efforts of many brilliant researchers, and we now understand the mechanics, the biochemistry, and the genetics of many of the ways in which cells can die. This knowledge gives us the resources to alter the fates of many cells. However, not all cells respo...
Article
Full-text available
Cell death is prominent in gametogenesis and shapes and sculpts embryos. In non-mammalian embryos one sees little or no cell death prior to the maternal-zygotic transition, but, in mammalian embryos, characteristic deaths of one or two cells occur at the end of compaction and are apparently necessary for the separation of the trophoblast from the i...
Chapter
Embryonic development and differentiation to adult form depends on orchestration of cell division and death. In embryos, programmed death sculpts form, opens lumens, separates or splits tissue layers, allows tissue layers to fuse and removes vestigial organs. Both the central nervous and immune systems overproduce cells and destroy those that do no...
Article
Full-text available
Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as /`accidental cell death/' (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correl...
Article
Full-text available
Flaviviruses, ss(+) RNA viruses, include many of mankind's most important pathogens. Their pathogenicity derives from their ability to infect many types of cells including neurons, to replicate, and eventually to kill the cells. Flaviviruses can activate tumor necrosis factor α and both intrinsic (Bax-mediated) and extrinsic pathways to apoptosis....
Data
Full-text available
Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.(2,3) There are many useful an...
Article
Full-text available
Sexual differences are only partially attributable to hormones. Cultured male or female cells, even from embryos before sexual differentiation, differ in gene expression and sensitivity to toxins, and these differences persist in isolated primary cells. Male and female cells from Swiss Webster CWF mice manifest sex-distinct patterns of DNA methylat...
Article
Full-text available
Impaired autophagic machinery is implicated in a number of diseases such as heart disease, neurodegeneration and cancer. A common denominator in these pathologies is a dysregulation of autophagy that has been linked to a change in susceptibility to cell death. Although we have progressed in understanding the molecular machinery and regulation of th...
Article
Full-text available
The story of cell death began with the origins of cell biology, including important observations by Elie (Ilya) Metchnikoff, who realized that phagocytes engulfed dying cells. Most of the early studies were observational. By the middle of the 20th C, researchers were beginning to explore how cells died, had recognized that cell death was a physiolo...
Article
Full-text available
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring au...
Article
Full-text available
Cell death and differentiation is a monthly research journal focused on the exciting field of programmed cell death and apoptosis. It provides a single accessible source of information for both scientists and clinicians, keeping them up-to-date with advances in the field. It encompasses programmed cell death, cell death induced by toxic agents, dif...
Article
Mechanical ventilation with hyperoxia is a necessary treatment for patients with respiratory distress. However, patients on mechanical ventilation have increased susceptibility to infection. Studies including ours have shown that reactive oxygen species (ROS), generated by exposure to prolonged hyperoxia, can cause a decrease in the phagocytic acti...
Article
Clusterin, originally isolated as testosterone-repressed prostate message-2 from regressing rat ventral prostate, has been identified with the process of active cell death (ACD). The clusterin gene product is a glycosylated dimer consisting of alpha and beta subunits, resulting from the 70-kilodalton preprotein. To determine its relationship with A...
Article
Programmed cell death in intersegmental muscles and labial glands of Manduca sexta is a type II form of active cell death, in which lysosomal destruction of cytoplasm is a prominent and early feature, and the collapse of the nucleus is late and relatively modest until the bulk of the cytoplasm has been eroded. The prominent features of this collaps...
Article
Full-text available
The labial gland of Manduca sexta is a valuable system to study the mechanisms of programmed cell death since the death of the gland is nearly synchronous and, except for the anterior duct, involves all of the tissue. The gland degenerates in 5 days during pupation. Our previous work documents a drop in total protein synthesis as the gland degenera...
Chapter
Embryonic development and differentiation to adult form depends on orchestration of cell division and death. In embryos, programmed death sculpts form, opens lumens, separates or splits tissue layers, allows tissue layers to fuse and removes vestigial organs. Both the central nervous and immune system overproduce cells and destroy those that do not...
Article
During metamorphosis of Manduca sexta, involution of labial glands follows an autophagic pathway towards programmed cell death (PCD). We looked for evidence of both caspase dependent and independent pathways of PCD by assaying for caspases -1, -2, -3, and -6, proteasomal protease, and cathepsins B & L, using fluorogenic substrates and aldehyde and...
Article
Full-text available
Cyclin-dependent kinase 5 (Cdk5) is similar to other Cdks but is activated during cell differentiation and cell death rather than cell division. Since activation of Cdk5 has been reported in many situations leading to cell death, we attempted to determine if it was required for any form of cell death. We found that Cdk5 is activated during apoptoti...
Article
Full-text available
The 2009 Annual Meeting of the International Cell Death Society (ICDS) (http://www.celldeath-apoptosis.org) was held in Johannesburg, South Africa, from 5 to 8 June 2009. More than 150 scientists from 23 countries participated in the meeting, which was organized by Zahra Zakeri, Richard A Lockshin, and Marianne J Cronje. Scientific presentations in...
Chapter
Cell death has long been known to be a normal part of embryonic development, typically sculpting the body, removing vestigial or sexually incongruent tissues, generating lacunae and separation of tissue layers, and playing other important roles in morphogenesis. The germ line manifests considerable death of supporting cells, presumptively defective...
Article
Full-text available
Sexual dimorphisms are typically attributed to the hormonal differences arising once sex differentiation has occurred. However, in some sexually dimorphic diseases that differ in frequency but not severity, the differences cannot be logically connected to the sex hormones. Therefore, we asked whether any aspect of sexual dimorphism could be attribu...
Article
Full-text available
Mammalian development is dependent on an intricate orchestration of cell proliferation and death. Deregulation in the levels, localization, and type of cell death can lead to disease and even death of the developing embryo. The mechanisms involved in such deregulation are many; alterations and or manipulations of these can aid in the detection, pre...
Article
Full-text available
Chapter
The history of our ideas is that, when a concept appears, it first gives a sense of clarity to a rather diffuse set of observations. For some time following the acceptance of the idea, new observations that support the hypothesis accumulate, while for several very human reasons, ambiguities are denied, tortuously forced into the hypothesis, or rule...
Article
Activation of autophagosomes in cell death has been described since the late 1950s as a form of cell death characterized by consumption of the bulk of the cytoplasm by lysosomal derivatives. However, it is not yet established that autophagy is a primary, causative mechanism of death rather than a response to initial problems. Methods to assess auto...
Article
Cell death was observed and understood since the 19th century, but there was no experimental examination until the mid-20th century. Beginning in the 1960s, several laboratories demonstrated that cell death was biologically controlled (programmed) and that the morphology was common and not readily explained (apoptosis). By 1990, the genetic basis o...
Article
Activation of autophagosomes in cell death has been described since the late 1950s as a form of cell death characterized by consumption of the bulk of the cytoplasm by lysosomal derivatives. However, it is not yet established that autophagy is a primary, causative mechanism of death rather than a response to initial problems. Methods to assess auto...
Chapter
Full-text available
Cell death was observed and understood since the 19th century, but there was no experimental examination until the mid-20th century. Beginning in the 1960s, several laboratories demonstrated that cell death was biologically controlled (programmed) and that the morphology was common and not readily explained (apoptosis). By 1990, the genetic basis o...
Article
Cell death is clearly an important factor in development, homeostasis, pathology, and in aging, but medical efforts based on controlling cell death have not become major aspects of medicine. There are several reasons why hopes have been slow to be fulfilled, and they present indications for new directions in research. Most effort has focused on the...
Book
Addresses the theoretical basis of science and is not just "watered-down Biology" Explains the most complex issues in a clear and non-technical manner Emphasizes the accessibility of scientific thinking and the excitement of science even to students who have feared or disliked what they considered to be science Relates the development of scientific...
Article
Full-text available
Cell death in animals is normally classified as type I (apoptotic), type II (autophagic) or necrotic. Of the biologically controlled types of death, in most embryos apoptosis is the most common, although in metamorphosis and in cells with massive cytoplasm type II is often seen, and intermediate forms are seen. For vertebrate embryos other than mam...
Article
Full-text available
Due to the worldwide increase in the number of older people in both developed and developing countries, there is a public health concern for dealing with age related diseases such as neurodegenerative diseases. There is little known about the dif- ference in neuronal cell responses between genders. Our understanding of the neuronal cell response re...
Article
Full-text available
The role and mechanism of cell death in early mammalian embryos is not well understood. In mouse embryos collected after fertilization and maintained in vitro until blastula formation, two instances of cell death are observed: the polar bodies and one or two cells near the equator, at the junction of the inner cell mass to the prototrophoblast. Inh...
Chapter
Development: The Basis for the Concept of Cell Death Naturally Occurring Cell Death in Embryos Genetic Control of Developmental Cell Death Functional Needs of Cell Death during Development Types of Cell Death Methods Useful to Study Cell Death in Development Detection of Cell Death by Morphology Detection of Cell Death by Light Microscopy Use of Ce...
Article
Cell death was observed and understood since the 19th century, but there was no experimental examination until the mid-20th century. Beginning in the 1960's, several laboratories demonstrated that cell death was biologically controlled (programmed) and that the morphology was common and not readily explained (apoptosis). By 1990 the genetic basis o...
Article
Cell death was observed and understood since the 19th century, but there was no experimental examination until the mid-20th century. Beginning in the 1960's, several laboratories demonstrated that cell death was biologically controlled (programmed) and that the morphology was common and not readily explained (apoptosis). By 1990 the genetic basis o...
Article
Full-text available
Cell death has been subdivided into the categories apoptosis (Type I), autophagic cell death (Type II), and necrosis (Type III). The boundary between Type I and II has never been completely clear and perhaps does not exist due to intrinsic factors among different cell types and the crosstalk among organelles within each type. Apoptosis can begin wi...
Article
Nonmammalian vertebrate embryos do not manifest apoptosis before gastrulation, and it has been suggested that their cells are inhibited from undergoing apoptosis. To study this interesting possibility, the zebrafish (Danio rerio) embryo is an excellent model. However, the appearance of apoptosis varies among species, and many components of cell dea...
Article
Full-text available
Many cells die with apoptotic morphology and with documented activation of an effector caspase, but there are also many exceptions. Cells frequently display activation of other proteases, including granzymes, lysosomal cathepsins, matrix metalloproteinases, and proteasomal proteases, and others display morphologies that are not fully consistent wit...
Article
A very common and the best understood of the mechanisms of physiological cell death is apoptosis, resulting from the activation, through either of two primary pathways, of site-specific proteases called caspases. There are, however, many other routes to cell death, prominently including autophagy and proteasomal degradation of critical constituents...
Article
There are many ways to measure apoptosis and other forms of programmed cell death in development. Once nonmammalian embryos have passed the midblastula transition, or much earlier in mammalian embryos, apoptosis is similar to that seen in adult organisms, and is used to sculpt the animal, fuse bilateral tissues, and establish the structure of the n...
Article
Full-text available
Activation or inactivation of members of the cyclin-dependent kinase family is important during cell cycle progression. However, Cdk5, a member of this family that was originally identified because of its high structural homology to Cdc2, is activated during cell differentiation and cell death but not during cell cycle progression. We previously de...
Article
Full-text available
Interest in the study of apoptosis grew with the recognition that it is a highly regulated process. Such a change in attitude allowed the intellectual and technical breakthroughs that led to the explosive development of this subject.
Article
The possibility of regulating apoptosis in cardiac disease is such an exciting prospect that the reader might wonder why there has not been more public clamor for antiapoptosis therapies in cardiovascular disease. Because heart muscle is considered to be nonrenewable tissue, scenarios can be imagined in which health food stores promote specific ant...
Article
Full-text available