Quality Control University

Contact Information:

SHILPA VASHIST

Home Address: **** ******* **** **, **********, NJ

Phone number: 732-***-****

e-mail: j1vuwk@r.postjobfree.com

Work eligibility: Permanent Resident (Green Card)

RESEARCH/WORK EXPERIENCE

University of Pennsylvania School of Medicine, Philadelphia, P A

Research Fellow (2008 –2010)

Application of remodeling enzymes to protein-misfolding disorders and neurodegenerative disorders (Alzheimer’s and Parkinson’s diseases)

Harvard Medical School and Massachusetts General Hospital, Boston, MA

Postdoctoral Fellow (2006 –2008)

Regulation and modulation of synapse function by micro RNAs (miRNAs) using genetic, biochemical, and fluorescent imaging techniques

Rutgers, The State University of New Jersey

Senior Research Associate (2005 –2006) Regulation of endocytic recycling in C.elegans

Yeast Protein Sciences, Inc. (YPS), CA (a start up, which spawned from my own research)

Research Scientist (2003)

Production of pharmaceutically useful, full-length properly folded human antibodies in yeast strains

EDUCATION

The Pennsylvania State University, University Park, P A, USA

2004: Ph.D., Biochemistry and Molecular Biology

Dissertation title: Quality control of protein folding in the endoplasmic reticulum

Jawaharlal Nehru University, Delhi, India

1996: M.Sc. Biotechnology

Thesis title: Analysis of upstream regions of ApoE gene associated with artherosclerosis

University of Delhi, Delhi, India

1994: B.Sc. (Honors Biochemistry)

PUBLICATIONS

Vashist S, Meinhardht N, Tammaro M, Shorter J. Variants of protein disaggregases, Hsp104 and ClpB efficiently disassemble disease causing Abeta -amyloids associated with Alzheimer’s disease (Manuscript in preparation)

DeSantis ME, Leung E, Sweeny EA, Jackrel ME, Cushman M, Neuhaus-Follini A, Vashist S, Sochor MA, Knight MN, and Shorter J. Operational Plasticity Enables Hsp104 to Disaggregate Diverse Amyloid and Non- Amyloid Clients (Submitted to Cell, June 2012)

Vashist S, Cushman M, Shorter J. Applying Hsp104 to protein-misfolding disorders. Biochemistry and Cell Biology. 2010, 88(1): 1-13

Chen CC, Schweinsberg PJ, Vashist S, Mareiniss DP, Lambie EJ, Grant BD. RAB-10 is required for endocytic recycling in the Caenorhabditis elegans intestine. Molecular Biology of the Cell. 2006, 17(3): 1286-97

Vashist S and Ng DT. Misfolded proteins are sorted by a sequential checkpoint mechanism of ER quality control. Journal of Cell Biology. 2004, 165(1): 41-52

Vashist S, Frank CG, Jakob CA, Ng DT. Two distinctly localized P-type ATPases collaborate to maintain organelle homeostasis required for glycoprotein processing and quality control. Molecular Biology of the Cell. 2002, 13(11): 3955-66

Vashist S, Kim W, Belden WJ, Spear ED, Barlowe C, Ng DT. Distinct retrieval and retention mechanisms are required for the quality control of endoplasmic reticulum protein folding. Journal of Cell Biology. 2001, 155(3): 355-68

John MV, Parwez I, Sivaram MV, Mehta S, Marwah N, Ali S. Analysis of VNTR loci in fish genomes using synthetic oligodeoxynucleotide probes. Gene. 1996, 172(2): 191-7

AREAS OF EXPERTISE

Cell and Molecular Biology, Genetics and Neuroscience

Areas of technical expertise:

Advanced Molecular biology methods

• Cloning and subcloning methods

• Generation of mutant libraries using chemical and PCR-based methods and their analysis

• Gene reporter assays

Protein Biochemistry

• Protein purification

• Denaturing and native immuno-precipitation of proteins

• Protein-protein interaction studies

• Analysis of protein folding using chemical modifiers

• Analysis of glycosylation status of proteins

• Assays for monitoring protein trafficking and turnover

• Standard biochemical and immunochemical assays including Western blotting and ELISA

Specialized techniques

• RNAi-mediated silencing of target genes

• Genotyping

• Fluorescent imaging

• Maintenance of cell cultures (HeLa, SH SY5Y and N2a cells) and viability/toxicity assays

• Microarray and genomic analysis

Other areas of expertise

• Rigorous experimental design and analytical skills

• Excellent communication, writing, editing and presentation skills

AWARDS

Pennsylvania State University Wadler Outstanding Doctoral Dissertation Award 2004 Pennsylvania State University Alumni Association Dissertation Award 2002

American Society for Cell Biology (ASCB) Predoctoral student travel award 2002 Pennsylvania State University Braddock award 2000

Jawaharlal Nehru University Merit Fellowship 1994 -1996

University of Delhi Silver Jubilee Merit award 1992

INVITED TALKS

The Carnegie Mellon University Yeast Meeting, 2004

Misfolded proteins are sorted by a sequential checkpoint mechanism of ER quality control.

American Society for Cell Biology (ASCB) annual meeting minisymposium, 2002

Topologically distinct surveillance systems in ER quality control

The Carnegie Mellon University Yeast Meeting, 2000

A transport and retrieval mechanism for misfolded proteins destined for ER-associated degradation

The Penn State Intercampus Yeast Meeting, 1999

A novel UPR-regulated P-type ATPase required for secretory protein biogenesis and quality control

PRESENTATIONS

American Society of Cell Biology Annual Meeting, 2003

ER quality control employs a sequential checkpoint mechanism for sorting misfolded proteins

American Society of Cell Biology Annual Meeting, 2001

Collaboration of two distinct P-type ATPases in secretory protein biogenesis and quality control

American Society of Cell Biology Annual Meeting, 2000

A transport and retrieval mechanism for misfolded proteins destined for ER associated degradation

PROFESSIONAL ACTIVITIES

Reviewer for Journals

Biochemical and Biophysical Research Communications (BBRC) Journal of General Microbiology

Indian Journal of Microbiology

Journal of Biological Chemistry

TEACHING EXPERIENCE

Teaching Assistant, Department of Biochemistry and Molecular Biology, Pennsylvania State University Microbiology laboratory course for Honors students - Fall semester, 1999

Biochemistry laboratory course for undergraduates - Spring semester, 2000

BRIEF RESEARCH SUMMARY

Doctoral research: Quality control of protein folding in the endoplasmic reticulum.

An impaired quality control system is the underlying cause of certain liver diseases, diabetes and neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. The understanding of the unfolded Protein Reygufisponse (UPR) signaling pathway and the protein degradation machinery has been greatly advanced in recent years through elegant studies performed in yeast and higher eukaryotes. However, the events that lead to recognition, sorting and targeting of aberrant proteins for degradation have remained more elusive. For addressing these issues, I designed a novel ER quality control substrate and characterized it in detail using genetic, biochemical and fluorescent imaging techniques. By coupling its analysis to that of other substrates, I uncovered that some misfolded proteins are retained in the yeast ER for degradation but surprisingly, others are transported from the ER to the Golgi apparatus. These proteins are then retrieved and brought back to the ER prior to degradation by the ubiquitin-proteasome system. In addition, I demonstrated that these retention and retrieval pathways for sorting of misfolded proteins monitor lesions in different domains of aberrant proteins and act sequentially, as in a system of checkpoints. Both publications from this work were described in the preview section by JCB and one of them was recommended by the Faculty of 1000 as a "must read" article.

During my doctoral work I also spent several months on research for a start-up pharmaceutical company, Yeast Protein Sciences, Inc. (YPS). This project was conducted at Penn State University in collaboration with YPS. The goal of this work was to produce pharmaceutically useful full-length, properly folded human antibodies in various yeast strains. It was a unique opportunity, which led me to gain valuable experience in conducting applied research directly aimed at producing a therapeutically useful product.

Postdoctoral research: (at MGH, Harvard university): Regulation and modulation of synapse function by micro RNAs (miRNAs).

The miRNAs impact multiple aspects of development, establishment and function of the neural circuits, therefore, absence of miRNA-mediated regulation leaves the nervous system vulnerable to many neurological disorders. To understand regulatory pathways in C.elegans and higher organisms for therapeutic intervention, in collaboration with another lab at Harvard, I applied multifaceted approaches in hippocampus neuronal cultures and worms to investigate complex relationships between physiology, synaptic outputs and observed behavior.

Postdoctoral research: (at University of Pennsylvania School of Medicine): Application of protein disaggregases to protein-misfolding disorders and neurodegenerative diseases.

I worked on developing tools to antagonize and reverse protein aggregation events connected with various neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease. Specifically, using in vitro assays and neuroblastoma cell lines, I explored ways to tailor naturally occurring protein disaggregases to effectively and selectively remodel and disassemble disease-causing amyloids

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