- Heat shock proteins research
- Reproductive System and Pregnancy
- Immune Cell Function and Interaction
- thermodynamics and calorimetric analyses
- Endoplasmic Reticulum Stress and Disease
- Multiple Sclerosis Research Studies
- Pregnancy and preeclampsia studies
- Physiological and biochemical adaptations
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- Viral Infectious Diseases and Gene Expression in Insects
- Sphingolipid Metabolism and Signaling
- Enzyme Structure and Function
- Microbial Inactivation Methods
- Inflammasome and immune disorders
- Advanced biosensing and bioanalysis techniques
- Circular RNAs in diseases
- Developmental Biology and Gene Regulation
- Mitochondrial Function and Pathology
- Phagocytosis and Immune Regulation
- Immunotherapy and Immune Responses
- Retinoids in leukemia and cellular processes
- Neurobiology and Insect Physiology Research
The Ohio State University Wexner Medical Center
2023-2025
University of Rochester Medical Center
2012-2023
University of Rochester
2007
Roswell Park Comprehensive Cancer Center
1994-2004
Northwestern University
1992-1995
Duke Medical Center
1988-1989
Duke University Hospital
1988-1989
Duke University
1988
The existence of multiple heat shock factor (HSF) genes in higher eukaryotes has promoted questions regarding the functions these HSF family members, especially with respect to stress response. To address questions, we have used polyclonal antisera raised against mouse HSF1 and HSF2 examine biochemical, physical, functional properties two factors unstressed heat-shocked human cells. We identified as mediator stress-induced gene transcription. displays DNA-binding activity, oligomerization,...
Transcriptional regulation of the human hsp70 gene in response to heat shock and other forms physiological stress occurs through activation transcription factor (HSF). Exposure cells a temperature 42 degrees C results transient HSF; its DNA-binding activity increases rapidly, plateaus, attenuates, during which intracellular levels increase. In an effort understand whether HSF is regulated negatively by hsp70, we have examined associates with hsp70. We show that activated interaction detected...
The existence of multiple heat shock factor (HSF) genes in higher eukaryotes has promoted questions regarding the functions these HSF family members, especially with respect to stress response. To address questions, we have used polyclonal antisera raised against mouse HSF1 and HSF2 examine biochemical, physical, functional properties two factors unstressed heat-shocked human cells. We identified as mediator stress-induced gene transcription. displays DNA-binding activity, oligomerization,...
Cancer treatments using ionizing radiation (IR) therapy are thought to act primarily through the induction of tumor cell damage at a molecular level. However, new concept has recently emerged, suggesting that immune system is required for effective IR therapy. Our work here identified interferon gamma (IFN-γ) as an essential cytokine efficacy Local (15 Gy) mice bearing Colon38, colon adenocarcinoma, decreases burden in wild-type animals. Interestingly, had no effect on IFNγKO mice. We...
Two distinct murine heat shock transcription factors, HSF1 and HSF2, have been identified. mediates the transcriptional activation of genes in response to environmental stress, while function HSF2 is not understood. Both factors can bind elements (HSEs) but are maintained a non-DNA-binding state under normal growth conditions. Mouse embryonal carcinoma (EC) cells only mammalian known exhibit HSE-binding activity, as determined by gel shift assays, even when at physiological temperatures. We...
Expression vectors have been constructed for a region of the human retinoic acid receptor-alpha (hRAR-alpha) and transferred into F9 embryonal carcinoma (EC) cells. When are overexpressed in cells, clones can be selected resistance to acid-induced differentiation. This effect is obtained even when hRAR-alpha expressed as beta-galactosidase fusion protein. Using component protein marker, overexpression has correlated with acid-resistance effect. The resistant no longer exhibit normal...
The Hox-1.3 gene is located on mouse chromosome 6 and has been previously shown to be expressed in embryos adults. In this study, we have examined the steady-state levels of transcripts undifferentiated differentiated F9 embryonal carcinoma cells. We find that there a rapid increase after differentiation induction level major 1.85-kilobase (kb) transcript peaks at 16-24 hr By using primer extension techniques 5' ends 1.85-kb mapped two sites induced Cellular fractionation RNA transfer blot...
One of the basic features inducible heat shock response is activation factor which results in rapid transcriptional induction genes. Although it widely considered that ubiquitous, several reports have indicated can vary both intensity and kinetics often a tissue-specific manner. Of interest been studies on expression genes brain, particularly observations certain cultured neuronal cells exhibit diminished response. We demonstrate transcription gene encoding 70-kDa protein (hsp70) upon Y79...
Although the mechanism(s) underlying failure of maternal immune system to reject semiallogeneic fetus have not been clearly defined, absence MHC class II antigen expression by fetal trophoblast cells very likely plays a critical role in maintenance normal pregnancy. However, regulation is poorly understood. Class transactivator (CIITA) transacting factor that required for both constitutive and IFN-γ-inducible gene transcription. In this report we demonstrate inability express antigens due...
Radiation therapy (RT) continues to be a cornerstone in the treatment for many cancers. Unfortunately, not all individuals respond effectively RT resulting clinically two groups consisting of nonresponders (progressive disease) and responders (tumor control/cure). The mechanisms that govern outcome radiotherapy are poorly understood. Interestingly, new paradigm has emerged demonstrating immune system mediates antitumor effects RT. Therefore, we hypothesized response following may dictate...
Multiple sclerosis (MS) is a demyelinating disease characterized by infiltration of autoreactive T cells into the central nervous system (CNS). In order to understand how activated, are able cross blood brain barrier, unique molecular characteristics pathogenic need be more thoroughly examined. previous work, our laboratory found autotaxin (ATX) upregulated activated in mouse model MS. ATX secreted glycoprotein that promotes cell chemokinesis and transmigration through catalysis...
Abstract As part of a study turnover rat olfactory receptor neurons we have been examining immunohistochemical expression members the 70 kD heat shock protein (HSP70) family in epithelium. Expression HSP70 is up‐regulated many cells following exposure to physiologically stressing conditions. Because dying are likely undergo some sort physiological stress before onset frank degeneration, hoped that anti‐HSP70 monoclonal antibodies would prove be useful markers for early stages neuron cell...
Trophoblast cells are unique because they do not express major histocompatibility complex (MHC) class II antigens, either constitutively or after exposure to interferon-γ (IFN-γ). The absence of MHC antigens on trophoblasts is thought play a critical role in preventing rejection the fetus by maternal immune system. inability genes primarily due lack transactivator (CIITA), transacting factor that required for constitutive and IFN-γ-inducible transcription. We, therefore, investigated...
Abstract Trophoblast cells (TBCs) form the blastocyst-derived component of placenta and play essential roles in fetal maintenance. The proinflammatory cytokine IFN-γ plays a central role activating cellular immunity, controlling cell proliferation, inducing apoptosis. is secreted by uterine NK during pregnancy mice required for proper formation decidual layer remodeling vasculature. Despite presence placenta, TBCs do not express either MHC class Ia or II Ags, are resistant to IFN-γ-mediated...
Abstract Rectal cancer ranks as the second leading cause of cancer-related deaths. Neoadjuvant therapy for rectal patients often results in individuals that respond well to and those poorly, requiring life-altering excision surgery. It is inadequately understood what dictates this responder/nonresponder divide. Our major aim identify factors tumor microenvironment drive a fraction radiotherapy. We also sought distinguish potential biomarkers would indicate positive response design...
Abstract MHC class II (Ia) Ag expression is inversely correlated with tumorigenicity and directly immunogenicity in clones of the mouse L1210 lymphoma (1 ). Understanding mechanisms by which regulated may facilitate development immunotherapeutic approaches for treatment some types leukemia. This study demonstrates that variation among due to differences transactivator (CIITA). Analysis stable hybrids suggests CIITA repressed a dominant mechanism II-negative clones. DNA-alkylating agents such...
Two distinct murine heat shock transcription factors, HSF1 and HSF2, have been identified. mediates the transcriptional activation of genes in response to environmental stress, while function HSF2 is not understood. Both factors can bind elements (HSEs) but are maintained a non-DNA-binding state under normal growth conditions. Mouse embryonal carcinoma (EC) cells only mammalian known exhibit HSE-binding activity, as determined by gel shift assays, even when at physiological temperatures. We...
Epstein-Barr virus (EBV) is deemed a necessary, yet insufficient factor in the development of multiple sclerosis (MS). In this study, myelin basic protein-specific transgenic T cell receptor mice were infected with murid gammaherpesvirus 68 (MHV68), an EBV-like that infects mice, resulting onset neurological deficits at significantly higher frequency than influenza or mock-infected mice. MHV68 exhibited signs including optic neuritis and ataxia which are frequently observed MS patients but...
I. INTRODUCTION All bacterial, plant, and animal cells must cope with rapid changes in their environment, including exposure to elevated temperatures, heavy metals, toxins, oxidants, bacterial viral infection, by a often dramatic change the patterns of gene expression, resulting synthesis family heat shock proteins molecular chaperones (Lindquist Craig 1988; Morimoto et al. 1990). Heat ensure survival under stressful conditions, which if left unchecked, lead irreversible cell damage untimely...