Ashok R Dinasarapu

Emory University | EU · Department of Neurology

Muscular diseases lead to muscle fiber degeneration, impairment of mobility, and in some cases premature death. Many of these muscular diseases are largely idiopathic. The goal of this study was to identify biomarkers based on their functional role and possible mechanisms of pathogenesis, specific to individual muscular disease. We analyzed the mus...

Glioblastoma (GBM) is the most common and malignant primary adult brain cancer. Allelic deletion on chromosome 14q plays an important role in the pathogenesis of GBM, and this site was thought to harbor multiple tumor suppressor genes associated with GBM, a region that also encodes microRNA-203 (miR-203). In this study, we sought to identify the ro...

Background: Macrophage activation by lipopolysaccharide and adenosine triphosphate (ATP) has been studied extensively because this model system mimics the physiological context of bacterial infection and subsequent inflammatory responses. Previous studies on macrophages elucidated the biological roles of caspase-1 in post-translational activation...

The human complement system is increasingly perceived as an intricate protein network of effectors, inhibitors and regulators that drives critical processes in health and disease and extensively communicates with associated physiological pathways ranging from immunity and inflammation to homeostasis and development. A steady stream of experimental...

The Signaling Gateway Molecule Pages (SGMP) database provides highly structured data on proteins which exist in different functional states participating in signal transduction pathways. A molecule page starts with astate of a native protein, without any modification and/or interactions. New states are formed with every post-translational modificat...

Background Marijuana’s putative anti-inflammatory properties may benefit HIV-associated comorbidities. How recreational marijuana use affects gene expression in peripheral blood cells (PBC) among youth with HIV-1 (YWH) is unknown. Approach YWH with defined substance use (n = 54) receiving similar antiretroviral therapy (ART) were assigned to one o...

Lesch–Nyhan disease (LND) is a neurodevelopmental disorder caused by variants in the HPRT1 gene, which encodes the enzyme hypoxanthine-guanine phosphoribosyl transferase (HGprt). HGprt deficiency provokes numerous metabolic changes which vary among different cell types, making it unclear which changes are most relevant for abnormal neural developme...

Background Immunosurveillance of the central nervous system (CNS) is vital to resolve infection and injury. However, immune activation within the CNS in the setting of chronic viral infections, such as HIV-1, is strongly linked to progressive neurodegeneration and cognitive decline. Establishment of HIV-1 in the CNS early following infection unders...

Numerous studies have linked Parkinson′s disease (PD) with low levels of uric acid (UA). Low UA has been associated with the risk of developing PD, and its progression and severity. The biological mechanisms underlying these relationships have never been firmly established. The most frequently proposed mechanism is that UA is an antioxidant. Low UA...

HIV preferentially infects α4β7+ CD4 T cells, forming latent reservoirs that contribute to HIV persistence during antiretroviral therapy. However, the properties of α4β7+ CD4 T cells in blood and mucosal compartments remain understudied. Employing two distinct models of HIV infection, HIV‐infected humans and simian‐human immunodeficiency virus (SHI...

Dystonia is characterized by involuntary muscle contractions that cause debilitating twisting movements and postures. Although dysfunction of the basal ganglia, a brain region that mediates movement, is implicated in many forms of dystonia, the underlying mechanisms are unclear. The inherited metabolic disorder DOPA-responsive dystonia is considere...

Lesch-Nyhan disease (LND) is an inherited disorder caused by pathogenic variants in the HPRT1 gene, which encodes the purine recycling enzyme hypoxanthine–guanine phosphoribosyltransferase (HGprt). We generated 6 induced pluripotent stem cell (iPSC) lines from 3 individuals with LND, along with 6 control lines from 3 normal individuals. All 12 line...

Purpose 50-60% of neuromuscular-disease patients remain undiagnosed even after extensive genetic testing that hinders precision-medicine/clinical-trial-enrollment. Importantly, those with DNA-based molecular diagnosis often remain without known molecular mechanism driving different degrees of disease severity that hinders patient stratification and...

Dystonia is characterized by involuntary muscle contractions that cause debilitating twisting movements and postures. Although basal ganglia dysfunction is implicated in many forms of dystonia, the underlying mechanisms are unclear. Therefore, to reveal abnormal striatal cellular processes and pathways implicated in dystonia, we used an unbiased pr...

Human papilloma virus (HPV) causes a subset of head and neck squamous cell carcinomas (HNSCC) of the oropharynx. We combined targeted DNA-and genome-wide RNA-sequencing to identify genetic variants and gene expression signatures respectively from patients with HNSCC including oropharyngeal squamous cell carcinomas (OPSCC). DNA and RNA were purified...

There are many causes for cervical dystonia (CD), although most cases are idiopathic and a cause cannot be identified. The observation that 10-15% of cases have an affected family member has pointed to genetic causes, but known genes account for only a small fraction of all cases. The current manuscript describes a series of studies focusing on pot...

The results of the RV144 trial demonstrated that vaccination could prevent HIV transmission in humans and that longevity of anti-Env antibodies may be key to this protection. Efforts to improve upon the prime-boost vaccine regimen used in RV144 have indicated that booster immunizations can increase serum anti-Env antibody titers but only transientl...

There is considerable effort directed toward evaluating HIV-1 vaccine platforms to select the most promising candidates for enhancing mucosal HIV-1 antibody. The most successful thus far, the RV144 trial provided partial protection due to waning HIV-1 antibody titers. In order to develop an effective HIV vaccine, it may therefore be important to un...

DYT1 dystonia is an autosomal dominant early‐onset movement disorder characterized by involuntary muscle contraction causing abnormal postures and or movements. It is caused by a 3‐basepair deletion in the TOR1A gene, which encodes torsinA. The mechanisms causing neurological dysfunction remain obscure, but are thought to involve abnormal function...

Rapid development of information technology has promoted World Wide Web (WWW) as a main dissemination hub for many biological data and literature. However, most of the information remains inaccessible to the users due to lack of inter connectivity of the data or databases, or lack of common machine-readable data exchange formats. The recent adaptat...

High-throughput (HTP) technologies enabling the simultaneous measurement of thousands of genes, proteins, and metabolites offer new opportunities for understanding the complex mechanisms underlying physiology, health, and disease. Mining these large omics datasets (transcriptomics, proteomics, and metabolomics) has required addressing issues such a...

Properdin is currently the only known positive regulator of complement activation and stabilizes the alternative pathway C3 convertase (C3bBb). It is composed of multiple identical protein subunits, with each subunit carrying a separate ligand-binding site. Previous reports suggest that properdin function depends on multiple interactions between it...

Complement C2 is a single chain serum glycoprotein (110 kDa), which serves as the catalytic subunit of C3 and C5 convertases in the classical and lectin pathways. During complement activation, C2 is cleaved by classical (C1s) or lectin (MBL-associated serine protease-2; MASP-2) proteases into two fragments: C2b and C2a. C2a, a serine protease, in c...

Integrins are heterodimeric transmembrane (TM) glycoproteins containing one each of α and β subunit, which are held together by non-covalent forces. Integrin β2 (CD18) is the β subunit for four heterodimers: αDβ2, αXβ2, αMβ2 and αLβ2. Integrin β2 family plays an essential role in leukocyte recruitment and activation during inflammation. Structurall...

H-ficolin is a serum lectin synthesized (as a ~34 kDa polypeptide) predominantly by the liver and lung tissues and is one of the soluble pattern recognition receptors of the innate immune system. It is structurally similar to L- and M- ficolins, but is different in its tissue expression and binding affinities to pathogenic ligands. Ficolins have an...

MASP-1 (mannose/mannan binding lectin associated serine protease-1) is a serum protein (~79kDa poylpeptide) predominantly synthesized by the liver. It is an important player in the innate immune system and is mainly bound to multimeric pathogen recognition receptors such as mannose/mannan-binding lectin (MBL) and the three ficolins (M-ficolin, L-fi...

MAp44 is a ~44 kDa alternate splice product of MASP1 and is mainly expressed in the heart. Mannose/mannan binding lectin (MBL) associated serine proteases, MASP-1 and MASP-3 are other products of MASP1. Similar to MASP-1 (isoform 1 of MASP1, which represents the longest transcript), MAp44 has a C1r/C1s/Uegf/bmp1 (CUB) domain, calcium-binding EGF-li...

MASP-3 (mannose/mannan binding lectin (MBL) associated serine protease-3) is ~82 kDa protein generated through alternative splicing of the MASP1 gene. This gene also generates MASP-1 and MAp44 proteins. MASP-3 is bound to multimeric forms of pathogen receptors, such as MBL and the three ficolins. MASP-3 has two CUB, a calcium-binding EGF-like, a tr...

MASP-2 (mannose/mannan binding lectin (MBL) associated serine protease-2) is a serum protein predominantly synthesized by the liver as a ~75kDa protein and is one of the key molecules of the innate immune system. It is mainly bound to multimeric protein complexes, such as MBL, the three ficolins (M-ficolin, L-ficolin and H-ficolin) and collectin ki...

Studies of macrophage biology have been significantly advanced by the availability of cell lines such as RAW264.7 cells. However, it is unclear how these cell lines differ from primary macrophages, such as thioglycolate-elicited peritoneal macrophages (TGEM). We used the inflammatory stimulus Kdo2-Lipid A (KLA) to stimulate RAW264.7 and TGEM cells....

L-ficolin is a serum lectin synthesized (as a ~37 kDa polypeptide) predominantly by the liver, and is one of the key molecules of the innate immune system. It has an amino (N)-terminal cysteine-rich region, a middle stretch of a collagen-like sequence, and a fibrinogen-like domain in the carboxy (C)-terminus. Three identical polypeptides form a str...

Mannose/mannan-binding lectin (MBL) is a serum lectin synthesized (as a ~32 kDa peptide) by the liver and is one of the key molecules of the innate immune system. Each peptide has an N (amino)-terminal cysteine-rich region, a middle stretch of a collagen-like sequence, and a carbohydrate recognition domain (CRD) in the C (carboxy)-terminus. Three i...

Complement factor H (fH) is a single chain plasma glycoprotein (approximately 150 kDa in size), with 20 domains termed complement control protein (CCP) domains or short consensus repeats (SCR). The complement factor H gene (CFH) is located on chromosome 1q32 in the regulators of complement activation (RCA) gene cluster, adjacent to the genes that c...

Macrophage inflammation and resulting increase in the levels of oxysterols plays an important role in the progression of cardiovascular diseases such as atherosclerosis. Upon stimulation with pathogen markers such as lipopolysaccharide (LPS), primary macrophages such as bone-marrow derived macrophages (BMDMs) as well as RAW 264.7 cells (a leukemia-...

Complement C5 is a 189 kDa protein synthesized in liver as a single-chain precursor molecule. The precursor molecule is then cleaved to a disulfide linked two-chain glycoprotein consisting of a 115 kDa (C5α) and a 75 kDa N-terminal (C5β) chain. C5 is present in all the three known complement activation pathways: classical, alternative and lectin. C...

Complement C1q subcomponent subunit A (C1qA) is one of the three components of C1q molecule. Functional C1q is composed of eighteen polypeptide chains: six C1qA chains, six C1qB chains, and six C1qC chains, which are arranged as six heterotrimers of ABC: (ABC)6. Each of the individual C1q polypeptide chain consists of a N-terminal region and a C-te...

Complement C3 is the central component of the human complement system. It is ~186 kDa in size, consisting of an α-chain (~110 kDa) and a β-chain (~75 kDa) that are connected by cysteine bridges. C3 in its native form is inactive. Cleavage of C3 into C3b (~177 kDa) and C3a (~9 kDa) is a crucial step in the complement activation cascade, which can be...

Macrophages play essential roles in immunity and lipid homeostasis. Studies of macrophage biology have been significantly advanced by the availability of cell lines such as RAW264.7 cells. However, it is unclear how these cell lines differ from primary macrophages, such as thioglycolate-elicited peritoneal macrophages (TGEM) and bone marrow-derived...

Lipids play an important role in physiology and pathophysiology of living systems. Several large-scale projects to characterize lipids and their functional roles have been initiated as exemplified by the LIPID MAPS effort. The LIPID MAPS is an exemplary systems biology project that measures cell-wide lipid changes in an attempt to reconstruct bioch...

The transcription start site (TSS) region shows greater variability compared with other promoter elements. We are interested to search for its variability by using information content as a measure. We note in this study that the variability is significant in the block of 5 nucleotides (nt) surrounding the TSS region compared with the block of 15 nt...

The information content (relative entropy) of transcription factor binding sites (TFBS) is used to classify the transcription factors (TFs). The TF classes are clustered based on the TFBS clustering using information content. Any TF belonging to the TF class cluster has a chance of binding to any TFBS of the clustered group. Thus, out of the 41 TFB...

The information content (relative entropy) of transcription factor binding sites (TFBS) is used to classify the transcription factors (TFs). The TF classes are clustered based on the TFBS clustering using information content. Any TF belonging to the TF class cluster has a chance of binding to any TFBS of the clustered group. Thus, out of the 41 TFB...

We have studied the core promoter region in five sets of promoter sequences by calculating the average mutual information content H (relative entropy). We have used specially constructed substitution matrices to calculate mono and dinucleotide replacements in a given block of aligned sequences. These substitution matrices use log-odds form of score...