Soumya Panigrahi

Case Western Reserve University | CWRU · Division of Infectious Diseases and HIV Medicine

While platelets are the essential mediators of hemostasis, they are being increasingly recognized for their potential of contributing to host defenses. Here, using immunofluorescent microscopy, western blot, and ELISA, we found that human β-defensin 3 (hBD-3), an important antimicrobial peptide produced by epithelial cells, can be detected in human...

SARS-CoV-2 infection can cause compromised respiratory function and thrombotic events. SARS-CoV-2 binds to and mediates downregulation of angiotensin converting enzyme 2 (ACE2) on cells that it infects. Theoretically, diminished enzymatic activity of ACE2 may result in increased concentrations of pro-inflammatory molecules, angiotensin II, and Brad...

Purpose of Review Systemic inflammation increases as a consequence of aging (inflammaging) and contributes to age-related morbidities. Inflammation in people living with HIV is elevated compared with the general population even after prolonged suppression of viremia with anti-retroviral therapy. Mechanisms that contribute to inflammation during agi...

Recent studies have implicated a role for adenosine‐dependent immunosuppression in head and neck tumor microenvironments. We describe expression of CD73, an enzyme critical to the generation of adenosine from extracellular AMP, in T cells and other cell types within human head and neck tumors. Flow cytometric analyses of tumor‐infiltrating cells in...

Atherosclerotic cardiovascular disease (ASCVD) remains an important cause of morbidity in the general population and risk for ASCVD is increased approximately 2-fold in persons living with HIV infection (PLWH). This risk is linked to elevated CD8 T cell counts that are abundant in atherosclerotic plaques and have been implicated in disease pathogen...

HIV infection is associated with an increase in the proportion of activated CD8 memory T cells (Tmem) that express CX3CR1, but how these cells are generated and maintained in vivo is unclear. We demonstrate that increased CX3CR1 expression on CD8 Tmem in people living with HIV (PLWH) is dependent on coinfection with human cytomegalovirus (CMV), and...

Cytotoxic CD4 T cells are linked to cardiovascular morbidities and accumulate in both human immunodeficiency virus (HIV) and cytomegalovirus (CMV) infections, both of which are associated with increased risk of cardiovascular disease. Here we identify CMV coinfection as a major driver of the cytotoxic phenotype – characterized by elevated CD57 expr...

Cytotoxic CD4 T cells are linked to cardiovascular morbidities and accumulate in both HIV and CMV infections, both of which are associated with increased risk of cardiovascular disease (CVD). In this study, we identify CMV coinfection as a major driver of the cytotoxic phenotype, characterized by elevated CD57 expression and reduced CD28 expression...

Circulating CD8+ T cells and monocytes are activated during human immunodeficiency virus (HIV) infection and colocalize in the aortas of simian immunodeficiency virus-infected nonhuman primates. We hypothesized that CD8+ T cells could exert a proatherosclerotic effect via paracrine actions on monocytes. We found that T-cell receptor-stimulated CD8+...

Immune nonresponder (INR) HIV-1-infected subjects are characterized by their inability to reconstitute the CD4+ T cell pool after antiretroviral therapy. This is linked to poor clinical outcome. Mechanisms underlying immune reconstitution failure are poorly understood, although, counterintuitively, INRs often have increased frequencies of circulati...

Untreated human immunodeficiency virus (HIV) infection is characterized by progressive CD4⁺ T-cell depletion and CD8⁺ T-cell expansion, and CD4⁺ T-cell depletion is linked directly to the risk for opportunistic infections and infection-associated mortality. With suppression of HIV replication by antiretroviral therapy, circulating CD4⁺ Tcell number...

Increases in inflammation, coagulation, and CD8 + T-cell numbers are associated with an elevated cardiovascular disease (CVD) risk in human immunodeficiency virus (HIV)–infected antiretroviral therapy (ART) recipients. Circulating memory CD8 + T cells that express the vascular endothelium-homing receptor CX3CR1 (fractalkine receptor) are enriched i...

In HIV-1-infected patients, increased numbers of circulating CD8+ T cells are linked to increased risk of morbidity and mortality. Here, we identified a bystander mechanism that promotes CD8 T cell activation and expansion in untreated HIV-1-infected patients. Compared with healthy controls, untreated HIV-1-infected patients have an increased popul...

A prothrombotic state and increased platelet reactivity are common in hyperlipidemia and oxidative stress. Lipid peroxidation, a major consequence of oxidative stress, generates highly reactive products including hydroxy-w-oxoalkenoic acids that modify autologous proteins generating biologically active derivatives. Phosphatidylethanolamine, the sec...

Key Points CAP-PEs, a novel type of oxidatively modified phospholipids, are present in vivo. CAP-PEs can activate platelets via TLRs by inducing a cross-talk between innate immunity and integrin activation signaling pathways.

Untreated human immunodeficiency virus (HIV) infection is characterized by progressive CD4+ T-cell depletion and CD8+ T-cell expansion, and CD4+ T-cell depletion is linked directly to the risk for opportunistic infections and infection-associated mortality. With suppression of HIV replication by antiretroviral therapy, circulating CD4+ Tcell number...

Recent epidemiological evidences indicate that arsenic exposure increases risk of atherosclerosis, cardiovascular diseases and microangiopathies in addition to the serious global health concern related to its carcinogenic effects. In experiments on animals, acute and chronic exposure to arsenic directly correlates cardiac tachyarrhythmia, and ather...

Background: HIV infection is associated with increased risk of thromboembolic and cardiovascular co-morbidities. While systemic inflammation is linked to cardiovascular risk, direct evidence of vascular inflammation and endothelial dysfunction is lacking. Methods: We examined by immunofluorescence microscopy thoracic aortas from 16 SIV or SHIV i...

Background: Persistent CD8 T cell expansion, low CD4/CD8 T cell ratios and heightened inflammation persist in antiretroviral therapy (ART)-treated HIV infection and are associated with increased risk of morbid outcomes. We explored the role of cytomegalovirus (CMV) infection in CD8 lymphocytosis and inflammation in ART-treated HIV infection. Meth...

HIV-1 infection is characterized by sustained CD8 T cell expansion that is linked to morbid outcomes even after HIV replication is controlled with antiretroviral therapy (ART). The drivers of this persistent CD8 expansion in HIV-1 infection are not well understood. Here we show that cycling frequency is increased in memory CD8 T cells in untreated...

In the era of highly effective antiretroviral therapy (ART), HIV-infected patients have a better long-term prognosis than ever; however, increased inflammation and coagulation in HIV infection is associated with an increased risk of cardiovascular and other morbidities. CD8 T cell expansion is characteristic of HIV infection and has been linked to...

IL-7 is a key homeostatic cytokine that provides signals for T cell survival and proliferation in vivo. In this article, we provide evidence that IL-7 utilization is enhanced by a novel mechanism of cytokine "recycling" during which T cells treated with rIL-7 are rapidly induced to express p-STAT5 and are subsequently able to recycle biologically a...

Monitoring of autophagy is challenging because of its multiple steps and lack of single befitting technique for a complete mechanistic understanding makes the task complicated. Here we evaluate the functionality of autophagy triggered by salinomycin (anti-cancer-stem cell agent) using flow cytometry and advanced microscopy. We show that salinomycin...

Majority of Chronic myeloid leukemia patients experience an adequate therapeutic effect from imatinib however, 26–37% of patients discontinue imatinib therapy due to a suboptimal response or intolerance. Here we investigated derivatives of apoptin, a chicken anemia viral protein with selective toxicity towards cancer cells, which can be directed to...

A prothrombotic state and increased platelet reactivity are common in pathophysiological conditions associated with oxidative stress. Lipid peroxidation, a major consequence of oxidative stress generates highly reactive products capable of modifying autologous proteins as well as lipids. Hydroxy-ω-oxoalkenoic acids and their carboxyalkylpyrrole (CA...

The molecular mechanism of Salinomycin's toxicity is not fully understood. Various studies reported that Ca(2+), cytochorme c, and caspase activation play a role in Salinomycin-induced cytotoxicity. Furthermore, Salinomycin may target Wnt/β-catenin signaling pathway to promote differentiation and thus elimination of cancer stem cells. In this study...

Rationale: A prothrombotic state and increased platelet reactivity are common in pathophysiological conditions associated with oxidative stress and infections. Such conditions are associated with an appearance of altered-self ligands in circulation that can be recognized by Toll-like receptors (TLRs). Platelets express a number of TLRs, including...

Kindlin-3 is a novel integrin activator in hematopoietic cells, and its deficiency leads to immune problems and severe bleeding, known as leukocyte adhesion deficiency III (LAD-III). Our current understanding of Kindlin-3 function primarily relies on analysis of animal models or cell lines. To understand the functions of Kindlin-3 in human primary...

A prothrombotic state and increased platelet reactivity are common in pathophysiological conditions associated with oxidative stress and infections. Such conditions are associated with an appearance in circulation of non-self or altered-self ligands that are commonly recognized by toll-like receptors (TLR). Platelets express a number of TLR, includ...

In this study we have calculated a 3D structure of apoptin and through modeling and docking approaches, we show its interaction with Bcr-Abl oncoprotein and its downstream signaling components, following which we confirm some of the newly-found interactions by biochemical methods. Bcr-Abl oncoprotein is aberrantly expressed in chronic myelogenous l...

Apoptin structure coordinates. (TXT)

Apoptin structure coordinates. (TXT)

Coordinates of Apoptin docking to BcrAbl. (TXT)

Coordinates of Apoptin docking to BcrAbl. (TXT)

Coordinates of Apoptin docking to BcrAbl. (TXT)

Apoptin structure coordinates. (TXT)

of a paper presented at Microscopy and Microanalysis 2009 in Richmond, Virginia, USA, July 26 – July 30, 2009

Apoptin, a small protein from chicken anemia virus, has attracted great attention, because it specifically kills tumor cells while leaving normal cells unharmed. The subcellular localization of apoptin appears to be crucial for this tumor-selective activity. In normal cells, apoptin resides in the cytoplasm, whereas in cancerous cells it translocat...

The regulation of cell proliferation, cell death, and cell survival must be tightly controlled in multicellular organisms where different tissues fulfill specialized functions. Uncontrolled overgrowth of a single tissue or even organ within the organism would be fatal for the existence of the whole organism. Thus, in multicellular organisms, decisi...

Apoptin, a protein from the chicken anemia virus, has attracted attention because it specifically kills tumor cells while leaving normal cells unharmed. The reason for this tumor selectivity is unclear and depends on subcellular localization, as apoptin resides in the cytoplasm of normal cells but in the nuclei of transformed cells. It was shown th...

Obesity is an increasingly serious socioeconomic and clinical problem. Between (1/4)-(1/3) of population in the developed countries can be classified as obese. Four major etiological factors for development of obesity are genetic determinants, environmental factors, food intake and exercise. Obesity increases the risk of the development of various...

Stem cells are self-renewing multipotent progenitors with the broadest developmental potential in a given tissue at a given time. Normal stem cells in the adult organism are responsible for renewal and repair of aged or damaged tissue. Adult stem cells are present in virtually all tissues and during most stages of development. In this review, we in...

Apoptin, a small protein from chicken anemia virus, has attracted great attention, because it specifically kills tumor cells while leaving normal cells unharmed. The subcellular localization of apoptin appears to be crucial for this tumor-selective activity. In normal cells, apoptin resides in the cytoplasm, whereas in cancerous cells it translocat...

Acquisition of a complex immune system during evolution provided organisms with the most effective defense mechanism against “foreign&rdquo or “non-self&rdquo invaders. This efficient protection against pathogens, however, has been achieved at the expense of a higher risk for “self&rdquo-directed reaction or autoimmunity. Establishment of self-tole...

Acquisition of a complex immune system during evolution provided organisms with the most effective defense mechanism against "foreign" or "non-self" invaders. This efficient protection against pathogens, however, has been achieved at the expense of a higher risk for "self"-directed reaction or autoimmunity. Establishment of self-tolerance and homeo...

The partial cross-utilization of molecules and pathways involved in opposing processes like cell survival, proliferation and cell death, assures that mutations within one signaling cascade will also affect the other opposite process at least to some extent, thus contributing to homeostatic regulatory circuits. This review highlights some of the con...

This review describes our current understanding of telomere length polymorphism and organization in breast cancer cells. The key roles of the telomeric DNA protein complexes as protectors of chromosomal ends in normal and cancer cells are under much attention in current research, and here we review some of these issues. In general the functionality...

Experiments were designed to investigate a new concept aiming for induction of graft-vs-malignancy (GVM) effect prior to stem cell transplantation (SCT). Mismatched lymphocytes given pre-SCT will be followed by a selective elimination of alloreactive donor lymphocytes, thus avoiding lethal graft-vs-host disease (GVHD). Recipient mice treated with s...

Graft-vs-host disease (GVHD) is a serious complication of allogeneic stem cell transplantation (SCT) and donor lymphocyte infusion (DLI), for which no effective therapy exists. In our study, KRN7000, a synthetic analog of alpha-galactosylceramide, known for its ability to activate natural killer T cells, was tested for its ability to prevent onset...

The growing incidences of secondary malignancies in long-term survivors of childhood leukemia following allogeneic bone marrow transplantation (alloBMT) are increasingly being reported. Among the late complications of conventional myeloablative alloBMT, the occurrence of secondary malignant solid tumors is of major concern. Secondary malignant and...

Allogeneic bone marrow or blood stem cell transplantation (BMT) represents an important therapeutic tool for treatment of otherwise incurable malignant and non-malignant diseases. Until recently, autologous and allogeneic bone marrow or mobilized blood stem cells transplantation were used primarily to replace malignant, genetically abnormal or defi...

Allogeneic immunocompetent splenocytes were tested for their ability to exert a GVT effect in a murine model of liver metastasis. Mammary carcinoma cells originating from an H-2(d) mouse were inoculated through the PV of F(1) (H-2(d/b)) mice, to mimic clinical hepatic involvement in malignant disease. Cell therapy was given either locally (PV) or s...

Allogeneic bone marrow transplantation (BMT) or blood stem cell transplantation represents an important therapeutic tool for the treatment of otherwise incurable malignant and nonmalignant diseases. Until recently. autologous and allogeneic BMT or mobilized blood stem cell transplantation was used primarily to replace a malignant, genetically abnor...

Allogeneic bone marrow transplantation (BMT) represents an important therapeutic tool for treatment of otherwise incurable malignant and non-malignant diseases. Until recently, myeloablative regimens were considered mandatory for eradication of all undesirable host-derived hematopoietic elements. Our preclinical and ongoing clinical studies indicat...

Fungal arthritis and osteomyelitis are rare and documented mainly in immunocompromised or neutropenic patients. Patients receiving therapeutic immunosuppression for organ transplants have also reported to suffer from aspergillus osteoarthritis. We describe two patients with aspergillus arthritis of the knee joint following fludarabine-based non-mye...

Allogeneic cell therapy, or donor lymphocyte infusion (DLI), following allogeneic bone marrow or blood stem cell transplantation (BMT) introduced at Hadassah in Jerusalem in early 1987 was already shown to be effective for treatment and prevention of relapse following maximally tolerated doses of chemoradiotherapy (1–3). Starting more than 5 years...

We have developed non-myeloablative stem cell transplantation (NST), using Fludarabine-based regimen (30 mg/m2/day × 6) in conjunction with either oral Busulfan (4 mg/Kg/day × 2) or higher doses in children due to rapid pharmakotinetics; Cytoxan (5 mg/Kg/day × 2) in Fanconi's anemia or 60 mg/Kg × 2 in severe aplastic anemia with ATG (fresenius) (5...