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Hello! My name is Maria Nicole Nedwidek, and I just completed a research fellowship in Cancer Biology at the Harvard Medical School - Massachusetts General Hospital Department of Molecular Biology.


Take a look at a recent profile of me in the Beacon Hill Times.


I am excited to be starting as an International Baccalaureate Advanced Placement Biology Teacher in the fall of 2003 at the Dwight School.


My current resume and CV is displayed at the end of this page, beneath my email link.


To view my recent submission of a Human Gene involved in cell division to the NIH National Center for Biotechnology Information, Click here.

To read my two recent publications on the Ras protein and oncogenesis, Click here

and Click here.

To read my publication entitled "Minimized Protein Structures: A Little Goes A Long Way" in the Proceedings of the National Academy of Sciences, Click here.


On January 15, 1999, I received my Ph.D. in Molecular Biology from the Department of Molecular Biology at Princeton University.


My doctoral dissertation, completed in Michael Hecht's lab in the Chemistry Department at Princeton involved the de novo design of proteins that can perform a function in vivo. The goal was to understand the relationship between structure and function at the molecular level in living things by building a library of rationally designed proteins from scratch. An analysis of the relationships between primary amino acid sequence, structure and function, and of the design elements that are necessary and sufficient for building well-folded proteins is presented in my doctoral dissertation, entitled Rational Combinatorial Design Suggests an Evolutionary Approach for Building Proteins.


I received my Master of Arts degree from Princeton University in June of 1994 for completing my qualifying exams in defense of a research proposal on Designing Novel DNA Binding Proteins.


I received my Bachelor of Science degree in Biology from the Massachusetts Institute of Technology in June of 1992. During the course of my four years there, I did research in developmental biology of the fruit fly Drosophila melanogaster under Dr. Terry Orr-Weaver at the Whitehead Institute, and also under Dr. Donald Rio and Dr. Hermann Steller. I spent my summers before graduate school working at New York University Medical Center, also in Drosophila biology, under Dr. Roger Karess.


I grew up in New York City, and graduated from Stuyvesant High School in June of 1988. During my stay at Stuyvesant, I completed a Science Talent Search Project at Hunter College for the 47th Westinghouse Science Talent Search, and my work placed in the top 300 competitors.

If you want to drop me a line, my email address is: mia@molbio.mgh.harvard.edu.

Click on my email address above to send me mail. I would love to hear from you!


Below is my current resume and CV.


Maria Nicole Nedwidek, Ph.D.

E-mail: mia@molbio.mgh.harvard.edu
Web: http://xanadu.mgh.harvard.edu/avruchweb/maria/index.html

EDUCATION

Harvard University School of Medicine
Massachusetts General Hospital
Boston, MA 02114
Research Fellowship in Cancer Genetics - Dept. of Medicine
appointed to faculty September 1999.

Princeton University
Princeton, NJ 08544
Doctor of Philosophy degree in Molecular Biology awarded January 1999.

Princeton University
Princeton, NJ 08544
Master of Arts degree in Molecular Biology awarded June 1994.

Massachusetts Institute of Technology
Cambridge, MA 02139
Bachelor of Science degree in Biology awarded June 1992.
Grade Point Average: 4.4 out of 5.0

Stuyvesant High School
New York, NY 10009
High School Diploma awarded June 1988.
Grade Point Average: 95.45 %

PUBLICATIONS AND PRESENTATIONS

Nedwidek, M. N. and Hecht, M. H. (1997). Minimized protein structures: A little
goes a long way. Proceedings of the National Academy of Sciences USA
v. 94, no. 19, pp. 10010-10011.

Nedwidek, M. N. (1999). Rational Combinatorial Design Suggests an Evolutionary
Approach for Building Proteins. Ph.D. Dissertation, Department of
Molecular Biology, Princeton University, Princeton, NJ, 08544.
Avruch, J. (presenter), Khokhlatchev, A., Nedwidek, M., Tzivion, G., Vavvas, D., 
Zhang, X-f. (2000) Ras Regulation of Protein Kinases. 25th European
Symposium on Hormones and Cell Regulation: Protein Kinase Cascades in
Signal Transduction; Nunez Lecture, September 2000, Alsace, France.
web: http://www.dcb-glostrup.dk/kinase/symposium_2000/abstr_4.htm

Ortiz-Vega, S., Khokhlatchev, A., Nedwidek, M., Zhang, X-f., Dammann, R.,
Pfeifer, G.P., and Avruch, J. (2002).  The putative tumor suppressor
RASSF1A homodimerizes and heterodimerizes with the Ras-GTP binding
protein Nore1. Oncogene v. 21, no. 9, pp. 1381-1390.

Khokhlatchev, A., Rabizadeh, S., Xavier, R., Nedwidek, M., Chen, T., Zhang, X-f.,
Seed, B., and Avruch, J. (2002)  Identification of a Novel Ras-Regulated
Proapoptotic Pathway.   Current Biology v. 12, no. 4, pp. 253-265.

AWARDS AND HONORS

RESEARCH AND
TEACHING EXPERIENCE

Research Fellowship at Harvard Medical School, Mass General Hospital, Sept. 1999-present
Post-Doctoral Cancer Research: Identifying the functions of eukaryotic genes in
and related to the Ras pathway for oncogenesis using in vivo & in vitro techniques.
Identifying functions for signal transduction (S.T.) gene products involved in the
regulation of mitosis by protein phosphorylation.

Mentorship/teaching: Science in the Classroom/Timilty Middle School/Boston,Nov.2002-present

Designed and executed hands-on lessons on digestion and enzyme biochemistry for
80 6th graders; Consulted in curriculum design; Judged Science Fair;
more lessons/curriculum development planned and executed.

Ph.D. Thesis Research under Dr. Michael Hecht, Princeton U., June 1993-Jan. 1999
Masters Degree awarded in June 1994 for defense of a research proposal on
"Building a Collection of Novel DNA Binding Proteins".  Research toward
the Ph.D. degree focused on understanding the primary determinants of
protein folding with the ultimate goal of designing proteins of specified
structures that have clinically therapeutic benefits.  Doctoral Dissertation
completed Jan. 15, 1999 is entitled Rational Combinatorial Design Suggests
an Evolutionary Approach for Building Proteins.
Concurrent (June 1997-Jan.1999) with pursuit of PhD, I was Lab manager
of day-to-day operations.

Graduate research under Dr. Austin Newton, Princeton U., spring 1993
Deletion analysis of DivL cellular differentiation gene of bacterium
Caulobacter crescentus.

Graduate research under Nobel Laureate Dr. Eric Wieschaus, Princeton U., fall 1992
Studied the patterned expression of the alkaline phosphatase enzyme
(thought to be involved in cell adhesion) in the early stages of Drosophila 
embryogenesis.

Teaching & Research Assistantship in Core Lab course at Princeton U., Jan.1999-May 1999
Assisted Dr. Alison Gammie with an extensive semester-long advanced course
in the
practice and techniques of molecular biology research.  Prepared reagents
and
maintained laboratory for 80 students and assisted in the planning, grade
distribution,
and administration of the course.  Techniques covered in the course
included routine
DNA preparation, cloning and sequencing.  Methods in yeast
genetics and protein
analysis were applied to the genetic analysis of mismatch
repair genes in the yeast
S. cerevisiae that are implicated in colon cancer in humans.

Mentoring of Princeton U.  Ph.D. and undergraduate students, Jan. 1998-May 1999
Trained graduate student in expression and purification of protein library
candidates and charged her with mentoring an undergraduate; trained
undergraduate student in molecular cloning techniques involved in PCR-based
mutagenesis and orchestrated research plan for the completion of his
Bachelors thesis in Chemistry at Princeton U.; trained undergraduate in
phage library screening techniques, routine microbiology, transformation of
E. coli, protein purification and expression, Western Blotting, and approaches
for man-made protein library design: supervised in-depth the writing of her
Junior Research Paper (May 1998) and of her senior thesis (May 1999).

Graduate Teaching Assistantship (TA) in Undergrad Biochemistry, Princeton U., fall 1994
Taught basic macromolecular structure (nucleic acids and proteins),
acid-base biochemistry, carbohydrate, lipid and protein metabolism;
tutored individually and graded exams.

Graduate TA in Undergraduate Molecular Biology Lecture and Lab, Princeton U., spring 1993
Taught basic molecular biology principles in class and one-to-one;
ran structured lab exercises on bacterial growth, DNA work, and 
developmental biology; graded exams and lab reports.

High School mathematics tutor for pre-high schoolers under Dr. A. Lefkowitz, summer 1992
Taught algebra, geometry and basic math in class and after hours; 
proofread, corrected and wrote exams.  All of my students successfully 
entered Stuyvesant H. S. after entrance exams.

TECHNICAL EXPERTISE

FURTHER RESEARCH,
WORK EXPERIENCE AND 
PUBLIC SERVICE

Undergraduate research under Dr. R. Karess, NYU Medical Center, NYC, summer 1991
Used RNA transcript analysis in an attempt to understand the genetic
structures of three alleles of a Drosophila melanogaster cell division
cycle mutation called rough deal (rod).


Undergraduate research under Drs. H. Steller & D. Rio, Drosophila Project Lab, MIT, 1991

Searched the Drosophila genome on the molecular level for the coding 
region of a protein called pleiotrophin, known to be critical for cell 
division and nerve cell outgrowth in mammals.

Undergraduate research under Dr. R. Karess, NYUMC Summer Undergraduate Research Program in Cellular and Molecular Biology, summer 1990
Helped to characterize a Drosophila cell division cycle mutation called
spaghetti-squash (sqh), known to inhibit cytokinesis, as a leaky allele
on both the molecular and cytological levels.  Work acknowledged in
Cell, v. 65: pp. 1177-1189, by R.E. Karess et al., 1991.

Undergraduate research under Dr. Terry Orr-Weaver, Whitehead Institute, MIT, 1990
Helped to screen for alleles of a developmental maternal effect mutation
in Drosophila; helped to determine the effects of various genetic
deficiencies on Drosophila embryos.

Biology research project under Dr. Shirley Raps, Hunter College, CUNY, Nov. 1986 through Nov. 1987:
Award granted Jan. 1988 for Westinghouse Science Talent Search Competition
Studied the effects of the mutagen methyl methane sulfonate on the
growth of and pigment production in the cyanobacterium
 Microcystis aeruginosa.

High School Mathematics: tutored pre-Stuyvesant students under Dr. A.Lefkowitz, summer 1992
(see Research and Teaching Experience).

Editor-in-Chief of High School Biology Science journal (Bio-Med Times), 1986-1988
Published articles, proofread submissions, designed layout,
and raised funds for publication

Personal Assistant for Director of Creative Services at the New York Post, summer 1989

Service Volunteer at the Queensborough Public Library, summers 1985 and 1986

Junior Camp Counselor at the Manhattan Children's Museum, summer 1984

Ph.D. Thesis TITLE:

Rational Combinatorial Design Suggests An Evolutionary Approach for Building Proteins



Thesis Examination Details:

Name of Doctoral Degree Recipient: Maria Nicole Nedwidek
Name of Institution: Princeton University; Princeton, New Jersey
Name of Faculty Advisor: Dr. Michael H. Hecht
Name of Program Director and Primary Examiner: Dr. Thomas J. Silhavy
Remainder of Examining Committee: Dr. Clarence Schutt; Dr. Michael Cole


Thesis ABSTRACT:

This thesis explores the success of a rational library design approach called binary patterning that places hydrophobic amino acids at the core of a globular protein fold and hydrophilic amino acids at its exterior by establishing a particular periodicity of residues in the linear protein sequence. A library of 5 X 108 protein candidates patterned in this manner and designed to fold into three-helix bundles were displayed on bacteriophage and probed for their ability to form a discontinuous epitope that binds human Immunoglobulin G (IgG). The formation of this epitope was the measure of success for the design strategy. Of 2,000 and ultimately 100 selected candidates that were exhaustively screened, no true IgG-binders were found. The most salient explanation for this result is that the design strategy was not sufficient to achieve the desired fold in any measurable abundance by the methods employed. Design tactics that maintain the hydrophobicity of the protein core but also incorporate steric constraints and packing and would very likely produce a higher success rate are discussed. The ultimate purpose of this document is to understand what elements of rational design are necessary to achieve success at reproducibly designing particular and precise protein structures.


REFERENCES

Dr. Joseph Avruch, M.D.: Director of Diabetes Unit; Professor of Medicine, 
Harvard Medical School; MGH Dept. Molecular Biology; Boston, MA 02114;
avruch@molbio.mgh.harvard.edu (617) 726-6911

Professor Thomas J. Silhavy, Ph.D.: Director of Graduate Studies; 
Princeton University Dept. of Molecular Biology; Princeton,  NJ  08544; 
tsilhavy@molbio.princeton.edu (609) 258-5899

Professor Clarence E. Schutt, Ph.D., Former Director of Graduate Studies; 
Princeton University Dept. of Chemistry; Princeton,  NJ  08544; 
schutt@Princeton.edu (609) 258-4435

Professor Roger Karess, Ph.D., Director of Research, 
Centre de Génétique Moléculaire, CNRS; Ave de la Terasse; 91198 
Gif-Sur-Yvette, France; Roger.Karess@cgm.cnrs-gif.fr (33-1) 69-82-32-25