CURRICULUM VITAE
Sasi K. Chilukuri
The
The Center for Pharmaceutical Biotechnology and
The Department of Medicinal Chemistry and Pharmacognosy
Lab Phone: (312) 996-1687
Fax: (312) 413-9303
Email: schilu1@uic.edu
EDUCATION
Ph.D. Candidate Current
M.S. Chemistry May, 2000
B.S. (Hons) Chemistry May, 1998 University
of
HOMETOWN
GRADUATE RESEARCH
PROJECT
My research focuses on Human Non-Spherocytic Hemolytic Anemia (HNSHA) caused by Pyruvate Kinase Deficiency. Several point mutations in the pyruvate kinase gene have been identified in patients suffering from HNSHA. Most of the mutations result in a reduced turnover rate of the enzyme leading to the varying degrees of severity of the disease state. No therapeutic cure is currently available for HNSHA and patients are usually treated with frequent blood transfusions and very often undergo a splenectomy. However, these remedies fail to alleviate symptoms in severe cases. Although pyruvate kinase is a ubiquitous enzyme, in humans different isozymes exist which are differentially regulated by unique allosteric effector molecules. Our central hypothesis is that the allosteric sites of the enzyme may be the most suitable targets for finding lead therapeutic compounds. We aim at identifying small molecule compounds that will bind to the allosteric site of the mutant enzymes and restore their normal function. An analysis and comparison of the functional and structural differences between the wild type and the mutant enzymes is leading us towards understanding the molecular basis of pyruvate kinase deficiency specifically and the nature of allosteric structural transitions in general. We will use the results from the research as guidelines for the design of small molecules compounds that will serve as activators or inhibitors of the enzyme which may eventually serve as lead compounds of therapeutic importance.
EXPERIENCE
2000-2004
University of
Graduate Research Assistant under Dr. Andrew Mesecar. Research focuses on understanding the molecular basis of pyruvate kinase deficiency using enzyme kinetics and x-ray crystallography and on developing small molecule compounds as potential lead compounds using allosteric-site targeted drug design.
2000-2001
1999-2000
Master’s thesis under the supervision of Dr. Musti J. Swamy:
Studies on the interaction of phosphorylcholine with the major acidic protein from bovine seminal plasma, PDC-109.
Summer 1999
Summer Research Fellow under Prof. Santosh K. Kar, Center for Biotechnology. Isolation, purification and initial characterization of the plant toxin Gelonin from Gelonium sp.
1998-1999
St. Stephen’s College,
Undergraduate Research under supervision of Prof. S. V. Eswaran focused on reviewing the anti-hepatotoxic properties of Phyllanthus niruri.
AWARDS AND
SCHOLARSHIPS
2004 Edward Benes
Scholarship for Outstanding Graduate Students in Pharmacognosy,
2003 Received the American Heart Association Pre-Doctoral Fellowship for two years (2004-2006).
2003 Travel award from American Crystallographic Association to attend annual meeting July 2003.
2003 UIC Student Travel Award for presentation at the American Crystallographic Association annual meeting July 2003.
2002 Full scholarship from Argonne National Laboratory to attend the
MEMBERSHIPS AND
PROFESSIONAL AFFILIATIONS
American Association of Pharmaceutical Scientists (UIC-AAPS Student Chapter)
Former Chair and Chair-Elect of the Student Chapter.
American Crystallographic Association (ACA)
ABSTRACTS AND POSTER
PRESENTATIONS
- Sasi K. Chilukuri,
Bernard D. Sanstersiero, Andrew D. Mesecar.
(2004) “Functional Characterization of the Most Prevalent Mutations in Pyruvate Kinase associated
with Hemolytic Anemia” Midwest Enzyme Chemistry Conference.
- Sasi K. Chilukuri,
Bernard D. Sanstersiero, Andrew D. Mesecar.
(2004) “Allosteric Regulation of prevalent PK
mutations associated with Hemolytic Anemia.”
- Sasi K. Chilukuri,
Bernard D. Sanstersiero, Andrew D. Mesecar.
(2003) “Structure-function Studies of the most prevalent mutations in Pyruvate Kinase Associated
with Hemolytic Anemia.”
- Sasi K. Chilukuri,
Bernard D. Sanstersiero, Andrew D. Mesecar.
(2003) “Structure of Pyruvate Kinase with a Novel Allosteric
Activator identified via Computational Docking.” American Crystallographic
Association Annual Meeting.
- Sasi K. Chilukuri, Bernard D. Sanstersiero, Andrew D. Mesecar (2003) “Structure of Pyruvate Kinase with a Novel Allosteric Activator identified via Computational Docking.” UIC Pharmacological Sciences Research Symposium. May 16, 2003.
- Sasi K. Chilukuri,
Bernard D. Sanstersiero, Andrew D. Mesecar
(2003) “Structure of Pyruvate Kinase with a Novel Allosteric
Activator identified via Computational Docking.”
ORAL PRESENTATIONS
- Literature
Seminar. “Allosteric
regulation of Aspartate transcarbamylase
determined by small angle X-ray scattering”
- Seminar
for Center for Pharmaceutical Biotechnology. “Allosteric-Site-Targeting:
A new approach to drug design.”
CONFERENCES ATTENDED
ACA
Annual Meeting – Local Committee member July
2004
-Facilitated
Sessions
ACA
Annual Meeting July/August 2003
Annual
MIKI meeting (Medicinal Chemistry) April 2001, 2002, 2003, & 2004
PROFESSIONAL COURSES
COMPLETED
2002
INSTRUMENTATION
EXPERIENCE
HPLC, UV-VIS Spectrophotometry, Circular Dichroism, 96/384-well Plate Reader
APS Synchrotron:
Beamlines: SER-CAT
BIO-CARS
X-ray Equipment: In house system. Raxis IIc detector (Rigaku) on RU-200 rotation anode.
Raxis IV++ detector (Rigaku) with inverted phi
LABORATORY SKILLS AND
TECHNIQUES
Cloning
and Site-directed mutagenesis using expression
vectors
Optimization
of expression conditions
Protein
Purification- column chromatography
Enzyme
kinetics – Single cuvette and 96-well plate assays
Gel
chromatography
SDS
PAGE protein gels
Agarose DNA gels
Native
protein gels
Crystallization
Optimization
of growth conditions
Cryo conditions & Screening
Capillary
mounting
Structure
Determination via X-ray Crystallography using Molecular Replacement
COMPUTER KNOWLEDGE
Familiar
with:
TableCurve2D,
SigmaPlot (including Enzyme Kinetics Module)
Unix
(including editors vi and jot)
Denzo/Scalepack (x-ray crystallography processing)
Solve/Resolve
(x-ray crystallography)
CNS
(x-ray crystallography)
· (x-ray crystallography)
HKL2000,
Crystal Clear (x-ray crystallography)
Insight
II (structure visualization)