Sudheer Kumar Gara

Sudheer Kumar Gara
National Institutes of Health | NIH · Endocrine Oncology Branch

M.Tech., Ph.D

About

67
Publications
5,007
Reads
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1,482
Citations
Additional affiliations
May 2013 - present
National Cancer Institute (USA), National Institutes of Health
Position
  • Exploring novel molecular targets for Adrenocortical Carcinoma
May 2011 - April 2016
National Institutes of Health
Position
  • PostDoc Position
May 2013 - March 2015
National Institutes of Health
Position
  • PostDoc Position
Education
August 2005 - April 2010
University of Cologne
Field of study
  • Biochemistry
July 2002 - June 2005
Indian Institute of Technology Kanpur
Field of study
  • Biological Sciences and Bio-Engineering
June 2000 - May 2002
Pondicherry University
Field of study
  • Biotechnology

Publications

Publications (67)
Article
Objectives: Recent insights regarding mechanisms mediating stemness, heterogeneity, and metastatic potential of lung cancers have yet to be fully translated to effective regimens for the treatment of these malignancies. This study sought to examine complex epigenetic mechanisms underpinning the aggressiveness of SCLC, with a focus on understanding...
Article
Introduction: The cancer stem cell hypothesis explains the heterogeneity, drug resistance, and metastatic potential of Small Cell Lung Cancer (SCLC). To address limited surgical tissue availability, we developed an induced pluripotent stem cell (iPSC) model for investigating SCLC stemness mechanisms and potential novel therapies. Cigarette smoke co...
Article
Small Cell Lung Cancer (SCLC) has been designated a recalcitrant cancer and a priority by National Cancer Institute. Despite recent insights regarding mechanisms mediating stemness, heterogeneity, and metastatic potential, these advances have yet to be fully translated to effective regimens for the treatment of SCLC. Previously, we identified Addit...
Chapter
Approximately 3–9% of all nonmedullary thyroid cancers are familial. Familial nonmedullary thyroid cancer (FNMTC) may occur as part of a familial cancer syndrome (syndromic) or as the predominant or only feature being nonmedullary thyroid cancer (nonsyndromic). Most cases of FNMTC are nonsyndromic, accounting for approximately 95% of all FNMTC case...
Article
Full-text available
Background Diffuse pleural mesothelioma (DPM) is an aggressive therapy-resistant cancer with unique molecular features. Numerous agents have been tested, but clinically effective ones remain elusive. Herein, we propose to use a small molecule CBL0137 (curaxin) that simultaneously suppresses nuclear factor-κB (NF-κB) and activates tumor suppressor p...
Article
Esophageal cancer (EsC) is the sixth leading cause of cancer-related mortality worldwide. Esophageal squamous cell cancers (ESCC) typically arise in the upper and mid-esophagus, whereas esophageal adenocarcinomas (EAC) arise in the distal esophagus and gastroesophageal junction. Presently, epigenetic mechanisms contributing to initiation, progressi...
Article
Introduction: Malignant pleural mesothelioma (MPM) is an aggressive incurable cancer usually associated with asbestos exposure. MPM has unique molecular features such as wild-type p53 (>90% regardless of histology) and aberrantly activated NF-κB. A diverse spectrum of anti-MPM therapeutic agents have been trialed, but clinically effective ones rema...
Article
Full-text available
Familial non-medullary thyroid cancer (FNMTC) is a form of endocrine malignancy exhibiting an autosomal dominant mode of inheritance with largely unknown germline molecular mechanism. Hereditary nonpolyposis colorectal cancer syndrome (HNPCC) is another hereditary autosomal dominant cancer syndrome which, if proven to be caused by germline mutation...
Article
Full-text available
Background: Lynch syndrome (LS) is an autosomal dominant disease caused by germline mutations in mismatch repair genes (MMR), leading to the early manifestation of tumors characterized by microsatellite instability (MSI) in >3 family members across at least 2 generations. MSI is a rare event in thyroid cancer (TC), occurring in up to 2.5% of sporad...
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Full-text available
Background Although communal smoking of hookah via water pipes is perceived to be a safe alternative to cigarette smoking, the effects of hookah smoke in respiratory epithelia have not been well characterized. This study examined epigenomic and transcriptomic effects of hookah smoke relative to cigarette smoke in human respiratory epithelial cells....
Article
Objective: Ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) encodes a master regulator of DNA methylation that has emerged as an epigenetic driver in human cancers. To date, no studies have examined UHRF1 in malignant pleural mesothelioma (MPM). The present study was undertaken to explore the therapeutic potential of targeti...
Article
Full-text available
Recent evidence has implicated APOBEC3B (Apolipoprotein B mRNA editing enzyme catalytic subunit 3B) as a source of mutations in breast, bladder, cervical, lung, head, and neck cancers. However, the role of APOBEC3B in adrenocortical carcinoma (ACC) and the mechanisms through which its expression is regulated in cancer are not fully understood. Here...
Article
Purpose: Most aggressive thyroid cancers are commonly associated with a BRAFV600E mutation. Preclinical and clinical data in BRAF V600E cancers suggest that combined BRAF and MEK inhibitor treatment result in a response, but resistance is common. One mechanism of acquired resistance is through persistent activation of tyrosine kinase (TK) signalin...
Article
Full-text available
Nonsyndromic familial non-medullary thyroid cancer (FNMTC) represents 3–9% of thyroid cancers, but the susceptibility gene(s) remain unknown. We designed this multicenter study to analyze families with nonsyndromic FNMTC and identify candidate susceptibility genes. We performed exome sequencing of DNA from four affected individuals from one kindred...
Article
Background: Adrenocortical carcinoma is an aggressive malignancy with a low but variable overall survival rate. The role of in adrenocortical carcinoma is poorly understood. Thus, in this study we performed long noncoding RNA expression profiling in adrenocortical carcinomas, adrenocortical adenomas, and normal adrenal cortex. Methods: Long nonc...
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Full-text available
Background Aberrant methylation is a known cause of cancer initiation and/or progression. There are scant data on the genome‐wide methylation pattern of nonfunctioning pancreatic neuroendocrine tumors (NFPanNETs) and sporadic and hereditary NFPanNETs. Methods Thirty‐three tissue samples were analyzed: they included samples from sporadic (n = 9), v...
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Full-text available
Background: The BRAFV600E mutation is the most common somatic mutation in thyroid cancer. The mechanism associated with BRAF-mutant tumor aggressiveness remains unclear. Lysyl oxidase (LOX) is highly expressed in aggressive thyroid cancers, and involved in cancer metastasis. The objective was to determine whether LOX mediates the effect of the act...
Article
Full-text available
Adrenocortical cancer (ACC) is a rare cancer with poor prognosis and high mortality due to metastatic disease. All reported genetic alterations have been in primary ACC, and it is unknown if there is molecular heterogeneity in ACC. Here, we report the genetic changes associated with metastatic ACC compared to primary ACCs and tumor heterogeneity. W...
Article
Full-text available
Background: There are conflicting reports on whether familial nonmedullary thyroid cancer is more aggressive than sporadic nonmedullary thyroid cancer. Our aim was to determine if the clinical and pathologic characteristics of familial nonmedullary thyroid cancer are different than nonmedullary thyroid cancer. Methods: We compared patients with...
Chapter
Approximately 3–9% of all nonmedullary thyroid cancers are familial. Familial nonmedullary thyroid cancer (FNMTC) may occur as part of a familial cancer syndrome (syndromic) or as the predominant or only feature being nonmedullary thyroid cancer (nonsyndromic). Most cases of FNMTC are nonsyndromic, accounting for approximately 95% of all FNMTC case...
Article
Full-text available
Drug repurposing is an effective approach to identify active drugs with known toxicity profiles for rare cancers such as ACC. The objective of this study was to determine the anticancer activity of combination treatment for ACC from previously identified candidate agents using quantitative high-throughput screening (qHTS). In this study, we evaluat...
Article
Context Patients with vHL disease caused by a missense VHL mutation have a more severe phenotype compared with other VHL mutation types. Objective To define PNET aggressiveness according to VHL genotype. Design A prospective natural history study. Setting The NIH clinical center. Patients Patients with vHL disease, pancreatic manifestations, an...
Article
Background: Nonfunctioning pancreatic neuroendocrine tumors (NFPanNETs) may be sporadic or inherited because of germline mutations associated with von Hippel-Lindau disease (VHL) or multiple endocrine neoplasia type 1 (MEN1). The clinical behavior of NFPanNETs is difficult to predict, even in tumors of the same stage and grade. The authors analyze...
Article
PURPOSE: There is currently no standard therapy for anaplastic thyroid cancer (ATC) and poorly differentiated thyroid cancer (PDTC), which account for two-thirds of thyroid cancer deaths. Driver mutations in the PI3K/AKT and RAF/RAS/MEK/ERK pathways are common in ATC and PDTC. Histone deacetylases (HDACs) regulate cancer initiation and progression....
Article
Tumor suppressor genes and the immune system are critical players in inhibiting cancer initiation and/or progression. However, little is known about whether a tumor suppressor gene can function through both immune-dependent and -independent mechanisms. Retinoic acid receptor responder 2 (RARRES2) is transcriptionally downregulated in multiple cance...
Article
Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA Unequivocally, cumulative mutations are required for the development of cancer and many sources of mutagenic activity contribute to tumorigenesis. Recent evidence has implicated that a member of cytidine deaminase family, APOBEC3B (Apolipoprotein B mRNA editing enzyme,...
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Full-text available
To gain insight into the pathogenesis of adrenocortical carcinoma (ACC) and whether there is progression from normal-to-adenoma-to-carcinoma, we performed genome-wide gene expression, gene methylation, microRNA expression and comparative genomic hybridization (CGH) analysis in human adrenocortical tissue (normal, adrenocortical adenomas and ACC) sa...
Article
Full-text available
Background: Patients with Cushing's Syndrome (CS) and Conn's Syndrome with bilateral adrenal masses pose a dilemma. Uptake of 18F-FDG by hyperfunctioning adrenal glands has not been previously reported and may help lateralize. The aim was to determine if 18F-FDG PET/CT scan could identify hyperfunctioning adrenal masses and determine a biological...
Article
Full-text available
Familial nonmedullary thyroid cancer accounts for 3 to 9% of all cases of thyroid cancer, but the susceptibility genes are not known. Here, we report a germline variant of HABP2 in seven affected members of a kindred with familial nonmedullary thyroid cancer and in 4.7% of 423 patients with thyroid cancer. This variant was associated with increased...
Article
Full-text available
Adrenocortical carcinoma (ACC) is a rare but lethal malignancy without effective current therapy for metastatic disease. IL-13-PE is a recombinant cytotoxin consisting of human interleukin-13 (IL-13) and a truncated form of Pseudomonas exotoxin A (PE). The main objectives of this Phase I dose-escalation trial were to assess the maximum-tolerated do...
Article
one of the most aggressive human malignancies with a median survival time of less than one year. A better understanding of the molecular events involved in ATC initiation and progression that could be targeted for therapy is gravely needed. There is limited data on the role of miRNAs in ATC. Screening of miRNA expression profile in thyroid cancer s...
Article
Adrenocortical carcinoma (ACC) lacks diagnostic and prognostic biomarkers to guide treatment. A consistently dysregulated pathway in ACC is the IGF signaling pathway, specifically overexpression of IGF2, IGF-I-receptor, and IGFBP2. The objective of this study was to perform a comprehensive analysis of serum IGF and IGFBP levels and to determine the...
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Full-text available
Dominant and recessive mutations in collagen VI genes, COL6A1, COL6A2, and COL6A3, cause a continuous spectrum of disorders characterized by muscle weakness and connective tissue abnormalities ranging from the severe Ullrich congenital muscular dystrophy to the mild Bethlem myopathy. Herein, we report the development of a mouse model for dominant c...
Article
Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies but its genetic drivers remain little understood. In this study, we report losses in expression of the microRNA miR-30a which is downregulated in ATC compared to differentiated thyroid cancer and normal tissue. miR-30a downregulation was associated with advanced differenti...
Article
Forkhead box P3 (FOXP3) is a well-known molecular marker for regulatory T cells (Tregs) and is considered as a master regulatory transcription factor for the development, maturation and function of Tregs. Mutations in FOXP3 lead to severe immune deficiencies and cancer in human and mice. Administration of Foxp3-expressing Tregs drastically reduced...
Article
Full-text available
TGF-β is overexpressed in advanced human cancers. It correlates with metastasis and poor prognosis. However, TGF-β functions as both a tumor suppressor and a tumor promoter. Here, we report for the first time that genetic deletion of Tgfbr2 specifically in myeloid cells (Tgfbr2MyeKO) significantly inhibited tumor metastasis. Reconstitution of tumor...
Article
One great challenge in our understanding of TGF-β cancer biology and the successful application of TGF-β-targeted therapy is that TGF-β works as both a tumor suppressor and a tumor promoter. The underlying mechanisms for its functional change remain to be elucidated. Using 4T1 mammary tumor model that shares many characteristics with human breast c...
Article
Collagen VI is a major extracellular matrix (ECM) protein with a critical role in maintaining skeletal muscle functional integrity. Mutations in COL6A1, COL6A2 and COL6A3 genes cause Ullrich Congenital Muscular Dystrophy (UCMD), Bethlem Myopathy, and Myosclerosis. Moreover, Col6a1(-/-) mice and collagen VI deficient zebrafish display a myopathic ph...
Article
Recently, three novel collagen VI chains, α4, α5 and α6, were identified. These are thought to substitute for the collagen VI α3 chain, probably forming α1α2α4, α1α2α5 or α1α2α6 heterotrimers. The expression pattern of the novel chains is so far largely unknown. In the present study, we compared the tissue distribution of the novel collagen VI chai...
Article
Full-text available
Collagen VI is an extracellular matrix protein with critical roles in maintaining muscle and skin integrity and function. Skin abnormalities, including predisposition to keratosis pilaris and abnormal scarring, were described in Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM) patients carrying mutations in COL6A1, COL6A2, and...
Article
In a recent study the DVWA gene located on human chromosome 3p24.3 was identified as a susceptibility locus for knee osteoarthritis in Japanese and Chinese patients (Miyamoto, Y., Shi, D., Nakajima, M., Ozaki, K., Sudo, A., Kotani, A., Uchida, A., Tanaka, T., Fukui, N., Tsunoda, T., Takahashi, A., Nakamura, Y., Jiang, Q., Ikegawa, S., 2008. Common...
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Full-text available
Here we describe three novel collagen VI chains, α4, α5, and α6. The corresponding genes are arranged in tandem on mouse chromosome 9. The new chains structurally resemble the collagen VI α3 chain. Each chain consists of seven von Willebrand factor A domains followed by a collagenous domain, two C-terminal von Willebrand factor A domains, and a uni...
Article
Ras superfamily GTP-binding proteins regulate important signaling events in the cell. Ras, which often serves as a prototype, efficiently hydrolyzes GTP in conjunction with its regulator GAP. A conserved glutamine plays a vital role in GTP hydrolysis in most GTP-binding proteins. Mutating this glutamine in Ras has oncogenic effects, since it disrup...

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