Vadiraja Bhat, PhD.

Mutation in the SHANK3 human gene leads to different neuropsychiatric diseases including Autism Spectrum Disorder (ASD), intellectual disabilities and Phelan-McDermid syndrome. Shank3 disruption in mice leads to dysfunction of synaptic transmission, behavior, and development. Protein S-nitrosylation, the nitric oxide (NO•)-mediated posttranslational modification (PTM) of cysteine thiols (SNO), modulates the activity of proteins that regulate key signaling pathways. We tested the hypothesis that… Show more

Mutation in the SHANK3 human gene leads to different neuropsychiatric diseases including Autism Spectrum Disorder (ASD), intellectual disabilities and Phelan-McDermid syndrome. Shank3 disruption in mice leads to dysfunction of synaptic transmission, behavior, and development. Protein S-nitrosylation, the nitric oxide (NO•)-mediated posttranslational modification (PTM) of cysteine thiols (SNO), modulates the activity of proteins that regulate key signaling pathways. We tested the hypothesis that Shank3 mutation would generate downstream effects on PTM of critical proteins that lead to modification of synaptic functions. SNO-proteins in two ASD-related brain regions, cortex and striatum of young and adult InsG3680(+/+) mice (a human mutation-based Shank3 mouse model), were identified by an innovative mass spectrometric method, SNOTRAP. We found changes of the SNO-proteome in the mutant compared to WT in both ages. Pathway analysis showed enrichment of processes affected in ASD. SNO-Calcineurin in mutant led to a significant increase of phosphorylated Synapsin1 and CREB, which affect synaptic vesicle mobilization and gene transcription, respectively. A significant increase of 3-nitrotyrosine was found in the cortical regions of the adult mutant, signaling both oxidative and nitrosative stress. Neuronal NO• Synthase (nNOS) was examined for levels and localization in neurons and no significant difference was found in WT vs. mutant. S-nitrosoglutathione concentrations were higher in mutant mice compared to WT. This is the first study on NO•-related molecular changes and SNO-signaling in the brain of an ASD mouse model that allows the characterization and identification of key proteins, cellular pathways, and neurobiological mechanisms that might be affected in ASD Show less

Venkata Charepalli 1, Lavanya Reddivari 2, Sridhar Radhakrishnan 1, Elisabeth Eriksson 3, Xia Xiao 4, Sung Woo Kim 5, Frank Shen 6, Matam Vijay-Kumar 4 7, Qunhua Li 6, Vadiraja B Bhat 8, Rob Knight 9 10, Jairam K P Vanamala 11 12 13

1Department of Food Science, The Pennsylvania State University, University Park, Pennsylvania.
2Department of Plant Science, The Pennsylvania State University, University Park, Pennsylvania.
3Biotechnology, Applied Nutrition and Food Chemistry, Lund… Show more

Venkata Charepalli 1, Lavanya Reddivari 2, Sridhar Radhakrishnan 1, Elisabeth Eriksson 3, Xia Xiao 4, Sung Woo Kim 5, Frank Shen 6, Matam Vijay-Kumar 4 7, Qunhua Li 6, Vadiraja B Bhat 8, Rob Knight 9 10, Jairam K P Vanamala 11 12 13

1Department of Food Science, The Pennsylvania State University, University Park, Pennsylvania.
2Department of Plant Science, The Pennsylvania State University, University Park, Pennsylvania.
3Biotechnology, Applied Nutrition and Food Chemistry, Lund University, Lund, Sweden.
4Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania.
5Department of Animal Science, North Carolina State University, Raleigh, North Carolina.
6Department of Statistics, The Pennsylvania State University, University Park, Pennsylvania.
7Department of Medicine, The Pennsylvania State University Medical Center, Hershey, Pennsylvania.
8Agilent Technologies, Wilmington, Delaware.
9Department of Pediatrics, University of California, San Diego, California.
10Department of Computer Science and Engineering, University of California, La Jolla, California.
11Department of Food Science, The Pennsylvania State University, University Park, Pennsylvania. [email protected].
12The Penn State Hershey Cancer Institute, Hershey, Pennsylvania.
13Center for Molecular Immunology and Infectious Diseases, The Pennsylvania State University, University Park, Pennsylvania. Show less

Umesh T Sankpal 1, Susan B Ingersoll 2, Sarfraz Ahmad 2, Robert W Holloway 2, Vadiraja B Bhat 3, Jerry W Simecka 4 5, Liz Daniel 6, Ekamber Kariali 7, Jamboor K Vishwanatha 1 8, Riyaz Basha 9 10 11
Affiliations collapse
Affiliations
1Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth, TX, 76107, USA.
2Department of Gynecologic Oncology, Florida Hospital Cancer Institute, Orlando, FL, 32804, USA.
3Agilent Technologies, Inc., Wilmington, DE… Show more

Umesh T Sankpal 1, Susan B Ingersoll 2, Sarfraz Ahmad 2, Robert W Holloway 2, Vadiraja B Bhat 3, Jerry W Simecka 4 5, Liz Daniel 6, Ekamber Kariali 7, Jamboor K Vishwanatha 1 8, Riyaz Basha 9 10 11
Affiliations collapse
Affiliations
1Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth, TX, 76107, USA.
2Department of Gynecologic Oncology, Florida Hospital Cancer Institute, Orlando, FL, 32804, USA.
3Agilent Technologies, Inc., Wilmington, DE, 19808, USA.
4Pre-clinical Services, University of North Texas Health Science Center, Fort Worth, TX, 76107, USA.
5Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, TX, 76107, USA.
6MD Anderson Cancer Center Orlando, Orlando, FL, 32806, USA.
7Department of Biotechnology, Sambalpur University, Jyoti Vihar, Sambalpur, Odisha, 768019, India.
8Molecular and Medical Genetics, University of North Texas Health Science Center, Fort Worth, TX, 76107, USA.
9Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth, TX, 76107, USA. [email protected].
10Pre-clinical Services, University of North Texas Health Science Center, Fort Worth, TX, 76107, USA. [email protected].
11Molecular and Medical Genetics, University of North Texas Health Science Center, Fort Worth, TX, 76107, USA. [email protected]. Show less

S-nitrosation of proteins relevant to Alzheimer's disease during early stages of neurodegeneration.
Seneviratne U, Nott A, Bhat VB, Ravindra KC, Wishnok JS, Tsai LH, Tannenbaum SR.
1 Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
2 The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139;
3 Agilent Technologies, Inc., Wilmington, DE… Show more

S-nitrosation of proteins relevant to Alzheimer's disease during early stages of neurodegeneration.
Seneviratne U, Nott A, Bhat VB, Ravindra KC, Wishnok JS, Tsai LH, Tannenbaum SR.
1 Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
2 The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139;
3 Agilent Technologies, Inc., Wilmington, DE 19808;
4 Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 [email protected].

Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):4152-7. doi: 10.1073/pnas.1521318113. Epub 2016 Mar 24. Show less

Julia S. Gelman1
Jonathan Wardman2
Vadiraja B. Bhat3
Fabio C. Gozzo4
Lloyd D. Fricker12

1.Dominick P. Purpura Department of NeuroscienceAlbert Einstein College of MedicineBronxUSA
2.Department of Molecular PharmacologyAlbert Einstein College of MedicineBronxUSA
3.Agilent TechnologiesWilmingtonUSA
4.Institute of ChemistryUniversity of CampinasCampinasBrazil

RongMenga, Michael Gormley, Vadiraja B.Bhat, AnneRosenberg, Andrew A.Quongad
a
Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, United States
b
Agilent Technologies, Inc., United States
c
Thomas Jefferson University Hospital, United States
d
Department of Otolaryngology-Head & Neck Surgery, Thomas Jefferson University, United States

Shaiju K. Vareed,# 1 , ¤a Vadiraja B. Bhat,# 3 , ¤b Christopher Thompson, 3 Vihas T. Vasu, 1 Damian Fermin, 4 Hyungwon Choi, 3 Chad J. Creighton, 7 Sitaram Gayatri, 1 , 8 Ling Lan, 5 Nagireddy Putluri, 1 , ¤a Gagan Singh Thangjam, 1 Punit Kaur, 3 Mohsen Shabahang, 3 Judith G. Giri, 9 Alexey I. Nesvizhskii, 4 Alexander A. A. Asea, 3 Anil G. Cashikar, 1 , 2 Arundhati Rao, 3 , ¶ James McLoughlin, 6 , ¶ and Arun Sreekumar 1 , 6

1 Department of Biochemistry and Molecular Biology and Cancer… Show more

Shaiju K. Vareed,# 1 , ¤a Vadiraja B. Bhat,# 3 , ¤b Christopher Thompson, 3 Vihas T. Vasu, 1 Damian Fermin, 4 Hyungwon Choi, 3 Chad J. Creighton, 7 Sitaram Gayatri, 1 , 8 Ling Lan, 5 Nagireddy Putluri, 1 , ¤a Gagan Singh Thangjam, 1 Punit Kaur, 3 Mohsen Shabahang, 3 Judith G. Giri, 9 Alexey I. Nesvizhskii, 4 Alexander A. A. Asea, 3 Anil G. Cashikar, 1 , 2 Arundhati Rao, 3 , ¶ James McLoughlin, 6 , ¶ and Arun Sreekumar 1 , 6

1 Department of Biochemistry and Molecular Biology and Cancer Center, Medical College of Georgia, Augusta, Georgia, United States of America,
2 Center for Molecular Chaperones & Radiobiology, Medical College of Georgia, Augusta, Georgia, United States of America,
3 Department of Pathology, Scott & White Hospital, Temple, Texas, United States of America,
4 Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America,
5 Department of Biostatistics, Medical College of Georgia, Augusta, Georgia, United States of America,
6 Department of Surgical Oncology, Medical College of Georgia, Augusta, Georgia, United States of America,
7 Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, United States of America,
8 Illinois Institute of Technology, Chicago, Illinois, United States of America,
9 Tumor Bank Department of Pathology, Medical College of Georgia, Augusta, Georgia, United States of America,
Sun Yat-sen University Medical School, China
#Contributed equally.
* E-mail: ude.mcb@amukeers Show less