THE CHARLES A. DANA RESEARCH INSTITUTE FOR
SCIENTISTS EMERITI (RISE) AT DREW UNIVERSITY
Photo courtesy of Lynne DeLade
Baldwin Honors Students in Honors 202 Meet with RISE Nobel Prize Winner Bill Campbell
ANNUAL REPORT
JULY 1, 2015—JUNE 30, 2016
Overview
The birthdate of RISE is ambiguous—somewhere between 1979 and 1981, depending upon how
one interprets “birth.” Being sensitive to age, we have chosen 1981 as the origin and are now
making plans to celebrate our 35th anniversary with a symposium on September 20.
Since its inception RISE has mentored over 400 students in our research laboratories, and another
90 have participated in the RISE Science Seminar for Baldwin Honors students. We continue to
mentor many students during the summer, including 15 in the current DSSI program.
This is also the 30th year of our ResMed program (explained below). Over 4,000 students from
around the world have participated to date. This year 200 students attended including 70 from
New York City via live video.
Personnel
We are excited to have Dr. Marvin Bayne (photo on next page) as a new RISE Fellow. Marvin is
an accomplished molecular biologist and biochemist with a long history as a research leader at
Merck Research Laboratories and Schering-Plough Research Institute. He has established a lab at
Drew for research on C.elegans,awidelystudiedprimitiveorganism.Thelabshouldserveas
avaluablemodelsystemtoexaminealargerangeofbiologicalfunctionsinneurobiology
(e.g.,Alzheimer’sDisease,Parkinson’sDisease,nicotineaddiction),metabolicdisease(e.g.,
insulinsignalingandresistance,fataccumulation)andcancersignalingpathways.
Photo courtesy of Lynne DeLade
Marvin joins current RISE Fellows Bimal DasMahapatra (biochemist, virologist), Ron Doll
(organic chemist), Vince Gullo (organic chemist), John Eickmeyer (physicist), Andy Evans
(organic chemist, NMR specialist), Neal Connors (microbiologist), Arny Demain
(microbiologist), and myself (statistician); and RISE Associate Fellows Bill Campbell
(parasitologist) and Jim Miller (chemist). Another RISE Fellow, biochemist Chuck Lunn,
resignedtotakeapositioninindustry.
NilyaSchaberservesascoordinatorforboththeRISEandResMedprograms.Sheispictured
belowwithMrs.RubydeStevens,widowofthefoundingdirectorofRISE,GeorgedeStevens.
Photos courtesy of Lynne DeLade
FormanyyearsDr.SamKongsamut(above,right)hasbeenavaluedfriendandcontributor
to RISE activities. Sam, a man with many interests, ranging from neuroscience to
entrepreneurship,hasbeenaRISEVisitingScientistduringthespringsemester.Hismain
activityhasbeentomentorstudentsintheRISEHonorsSeminar,whichisanofferinginthe
BaldwinHonorsProgram.
RISE Talks
With help from Professor Minjoon Kouh of the physics department, we continue to sponsor the
RISE Talks Series on topics of general interest to science faculty and students as well as selected
local organizations and individuals outside of Drew. We were especially pleased to have had talks
this year by several highly accomplished women scientists working in New Jersey. Professor
Kouh himself gave a very timely talk on human vs. artificial intelligence shortly after the highly
publicized Go games between the world human Go champion and Google’s DeepMind (alphaGo)
program.
Baldwin Honors Science Seminar
RISE members served as mentors for the Honors 202 Science Seminar for the sixth time during
the spring semester. The 15 students in the class were all second-semester freshmen. Each one
was paired with a RISE mentor and spent the semester carrying out and communicating about an
in depth research project on topics such as: coral bleaching, multiple sclerosis treatment, self-injury
and pain, thorium as a source of energy, and cross-media measurement of audience activity. The
May 2016 issue of the Drew Review contains an article by Tyler Dorrity, C’18, that summarizes
his research done in last year’s class. Its title is “Natural defenses: reactivating the native immune
system to combat cancers through immune-checkpoint mediated pathways.” We hope that some
of this year’s projects will also appear in the Drew Review next year.
One of the many highlights of the 2016 class was a presentation by RISE Associate Fellow Bill
Campbell (see cover photo), who spoke to the students on Poem, Paint, and Parasite or how to
have a satisfying and productive time as an artist as well as a scientist. (Bill is an internationally
known parasitologist who has done just that!)
Drew Chemistry Professor, Alan Rosan, served as facilitator for the class for the third time and
once again did a masterful job.
Awards
Each year RISE has the opportunity to celebrate the accomplishments of some of the students
who have worked with us. The George deStevens Award for RISE Research honors the
memory of the founding director of RISE. The 2016 award was shared between Austin Larocca,
C’17 and Ian Pavlak, C’17. Austin’s research, under the guidance of Bimal DasMahapatra,
involves the culturing of mammalian cancer cell lines in order to assay them for functionality of
mutant p53 after introduction of novel compounds made at Drew. The goal is to restore p53
functionality as a tumor suppressor protein in malignant cells. Ian was honored for his work
with Ronald Doll on chemical compounds that will cross biological membranes, such as the
blood brain barrier. Such compounds could result in new drugs for the treatment of various brain
diseases.
Austin was also the recipient of the 2015-2016 academic year Novartis Science
Scholarship Award. The scholarship is funded by the Novartis Company and is administered by
the Independent College Fund of New Jersey, which supports undergraduate student research
projects at its member colleges and universities. Austin presented his results at the 2016 ICFNJ
Undergraduate Research Symposium on March 7.
The Sidney Udenfriend Prize, which honors the memory of the second director of RISE, was
awarded to Victoria Korn, C’16, a neuroscience major. The prize was presented to her in
recognition and appreciation of her leadership role, working with other Drew students, in the RISE
laboratory of Arnold Demain. Her project deals with platensimycin, a natural product anti-biotic
agent for fighting multi-drug resistance. Specifically, the team has been working to elucidate the
nutritional control of platensimycin biosynthesis by the filamentous bacterium Streptomyces
platensis.
Drew Stenger, C’17, received the Carol D. Litchfield Outstanding Student Poster
Presentation Award in the Fermentation/Cell Culture division at the annual meeting of the
Society for Industrial Microbiology and Biotechnology in Philadelphia. His participation at the
meeting was made possible by the Paolo Cucchi Fund of the Baldwin Honors Program. Stenger’s
research concerns a glucose auto-feed system for the production of glucaric acid by fermentation
of the bacteria E. coli. Neal Connors is his mentor.
Rebecca Ferreira, C’16, was awarded second place in the 68th Annual Undergraduate
Research Conference, hosted by the North Jersey section of the American Chemical
Society. Rebecca's presentation title was "Synthesis of allosteric stimulators of the mGluR4
glutamate receptor for potential therapies of CNS diseases." Rebecca recently joined the drug
discovery division of Pfizer Corp. as a bioanalytical chemist. Ron Doll was her mentor.
And I almost forgot: “we” received our first Nobel Prize! That is to say, our own Bill Campbell
received the 2015 Nobel Prize in Physiology or Medicine, along with Dr. Satoshi Omura of
Japan, for the work they and Bill’s Merck colleagues did that led to the discovery of ivermectin as
an amazingly effective treatment for river blindness. We are still trying to answer a follow-up
question from the administration: when will Drew receive its next Nobel Prize? Bill is shown on
the next page, left panel, with President MaryAnn Baenninger at a reception for him in the Ehinger
Center where she presented Bill with a plaque in his honor from the Board of trustees.
Photos courtesy of Lynne DeLade
Bill was further honored at Drew’s 2016 Commencement on May 14 with an honorary degree,
Doctor of Humane Letters, honora causa, also presented by President Baenninger (upper, right).
Support
We are most appreciative of the financial contributions we receive from a variety of “believers” in
what we do to educate the next generation of STEM (science, technology, engineering, and
mathematics) researchers. We are especially grateful to Mr. Joe Baker, C’69, who established The
William O. and Frances B. Baker RISE Fellowship in memory of his parents in 2014. We look
forward to awarding the first fellowship in a year or two.
Our summer student research activities in the DSSI program were supported by much appreciated
donations from Merck and Novo Nordisk. Previous contributions by Mrs. Ruby deStevens helped
us to support two DSSI students this summer.
A generous donation from Kalion, Inc., of Milton, MA, orchestrated by Neal Connors, allowed us
to purchase a refractive index protector which expands our capabilities for study of microbial
growth.
ResMed
The 30th annual ResMed: Residential School on Medicinal Chemistry and Biology in Drug
Discovery was held the week of June 5th. The ResMed program is a cornerstone of RISE. Over
4,000 students have participated in the program since its inception.
This year the school was held off campus at the Wyndham Hotel Hamilton Park and Conference
Center, about one mile from campus, because of the construction activity in the university’s dining
hall.
Interest in the course remains at a very high level: 134 students participated on site and another
70(!) viewed it at the Tri-Institutional Therapeutics Discovery Institute (Tri-I TDI) in New York
City. Tri-I TDI is an independent non-profit partnership of Memorial Sloan-Kettering Cancer
Center, Rockefeller University, and Weill Cornell Medical College, along with Takeda
Pharmaceutical Company, Ltd., a Japanese firm. Twenty four of the on-site students came from
ten foreign countries: Belgium, Canada, China, Denmark, Germany, India, Japan, South Korea,
New Zealand, and the United Kingdom. Eight came from Japan alone! The course was taught by
22 academic and industrial experts in various aspects of biology and medicinal chemistry in the
drug discovery process.
Special tributes were made to Dr. David Triggle from SUNY-Buffalo, who has lectured in ResMed
for 30 straight years, and to Dr. Christopher Haber, Zoetis, Inc., who has done the same for 15.
The ResMed keynote address was presented by Dr. Dennis Liotta, Executive Director of the Emory
Institute for Drug Development and Samuel Candler Dobbs Professor of Chemistry at Emory
University (photo, below right). Dr. Liotta is well known for the discovery of several marketed
anti-HIV drugs. He was introduced by President MaryAnn Baenninger and spoke about the
question “Is Academic Drug Development an Oxymoron?”
Photos courtesy of Lynne DeLade
The strong uptick in attendance this year reflects a number of important initiatives taken by the
ResMed organizing committee, co-chaired by RISE Fellows Vince Gullo and Ron Doll and Bill
Greenlee, President of MedChem Discovery Consulting, and Nilya Schaber, our RISE ResMed
Coordinator. The course continues to receive excellent reviews from the participants.
Looking Ahead
Last year we pointed out the growing importance of connections between RISE and external
companies and institutions. One highlight of the past two years has been our collaboration with
NovoBiotic Pharmaceuticals based in Cambridge, MA. This has resulted in two funded “hot topic”
research projects in the current DSSI program. We hope to be able to replicate this model with
other companies in the future!
One of our biggest challenges has been to attract women scientists to RISE, mainly because of
historical hiring patterns in industry. While Barbara Petrack, RISE Fellow Emerita, continues to
help us in various ways, we would benefit greatly by finding a new cohort of female research
scientists.
We now have our first student working with us from Drew’s INTO pathway program. We look
forward to attracting more as the program grows.
Invitation
For more information about RISE, please contact us at any time ([email protected] or
[email protected]) or visit our website www.drew.edu/rise. Even better, drop by for a personal visit
and tour!
Jon Kettenring
RISE Director
June 30, 2016
RISE Annual Report (July 1, 2015 – June 30, 2016)
Neal C. Connors, Ph.D.
Tenure in RISE: Fellow May 2015 – Present, Associate February 2012 – May 2015
Kalion, Inc., Chief Technical Officer, 2010 – present
Phoenix BioConsulting, LLC, Owner/President, 2009 – present
Bioprocess R&D, Senior Investigator, Merck & Co., 1991 – 2008
Ph.D. Microbiology, The Ohio State University, 1991
AREAS OF EXPERTISE AND RESEARCH INTERESTS:
Microbial Fermentation, Bioprocess Development, Industrial Microbiology, Renewable Fuels &
Chemicals, Natural Products
RESEARCH PROJECTS AND MENTORING ACTIVITIES:
Supervised/mentored the following students:
•
Drew Stenger – Junior: The biological production of glucaric acid: determining soluble
expression levels of myo-inositol oxygenase. (DSSI 2015, Fall 2015 research)
•
Sara Silvestri – Senior: Production of glucaric acid from sugar produced from waste
cardboard. (Fall 2015/Spring 2016 research)
•
Paul Loiugene – Junior: Chemical and biological formation of glucarolactones from glucaric
acid. (Fall 2015/Spring 2016 research)
•
Leslie Eyzaguirre-Mercado – Junior: Production of ethanol from sugar produced from waste
cardboard and the use of adaptive evolution to generate an improved yeast production strain.
(Spring 2016 research)
•
Erin Connors – rising Junior: Teixobactin analogue production by directed biosynthesis and
the use of methylation inhibitors (DSSI 2016).
•
Josephine Emanuelli – Freshman: Exploring the uses of bacteria in oil spill bioremediation
(Hon202, Spring 2016).
•
Alexandra Koeck – Freshman: A peer review on the sustainability of Keurig Green
Mountain single brew K-cup systems. (Hon202, Spring 2016)
OTHER PROFESSIONAL ACTIVITIES:
•
Continued collaboration on the biological production of glucaric acid with Prof Kristala
Prather (MIT, Chemical Engineering) and Kalion, Inc.
•
Collaboration with Avatar Sustainable Technologies (Fayetteville, NY) on the use of sugar
derived from waste cardboard as a fermentation substrate
•
Collaboration with Novobiotic Pharmaceuticals (Cambridge, MA) – with Dr. Vince Gullo –
on the production of analogues of the antibiotic teixobactin using directed biosynthesis and
methylation inhibitors.
•
Lecturer, Fermentation Technology – MIT Professional Education course (“Design of
Experiments: Statistical DOE Approach”)
•
Editorial Board, Journal of Industrial Microbiology and Biotechnology
•
Editorial Board, Enzyme and Microbial Technology
PUBLICATIONS and PRESENTATIONS:
Brockman IM, Stenger AR, Connors NC, Prather KLJ (2015) Improvement of glucaric acid
production in E. coli via dynamic control of metabolic fluxes. Metabolic Engineering
Communications. 2:109-116.
Connors N, Prather D, Watson A, Prather KLJ. (2015) Bioprocess-based production of glucaric
acid by recombinant E. coli strains. Society for Industrial Microbiology and Biotechnology
Annual Meeting and Exhibition, Philadelphia, PA
Stenger D, Connors N. (2015) Glucose auto-feeding for glucaric acid production by a
recombinant E. coli strain. Society for Industrial Microbiology and Biotechnology Annual
Meeting and Exhibition, Philadelphia, PA
MEMBERSHIP IN PROFESSIONAL SOCIETIES:
Society for Industrial Microbiology and Biotechnology
RISE RESEARCH RESULTS:
Glucaric Acid Production and Physiology
The work on glucaric acid is part of a materials transfer agreement (MTA) between Drew
University and Kalion, Inc., an angel investor-backed start-up company looking to
commercialize the biological production of glucaric acid. This MTA also facilitates the
collaboration with Prof. Kristala Prather (MIT, Chemical Engineering) whose group provides
metabolically engineered E.coli strains that produce glucaric acid from glucose. Glucaric acid
was listed in a 2004 DOE report as, “Top Value Added Chemicals from Biomass” and could
potentially serve as a functional replacement for petroleum-derived feedstock chemicals for the
production of materials such as polymers.
Drew Stenger presented a poster at the Society for Industrial Microbiology and Biotechnology
Annual Meeting (Philadelphia, PA) on the glucose “auto-feed” cultivation system he
implemented for the production of glucaric acid. For this poster presentation, Drew received the
Carol D. Litchfield Outstanding Student Poster Presentation Award in the Fermentation/Cell
Culture division. His participation at the meeting was made possible by the Paolo Cucchi fund
of the Baldwin Honors Program at Drew University.
This cultivation system has also become a central method in Prof. Prather’s lab for evaluating
glucaric acid production by new metabolically engineered strains. This has resulted in a joint
publication: Brockman IM, Stenger AR, Connors NC, Prather KLJ (2015) Improvement of
glucaric acid production in E. coli via dynamic control of metabolic fluxes. Metabolic
Engineering Communications. 2:109-116.
During the fall 2015 semester, Drew used his cultivation system to evaluate the expression of
myo-inositol oxygenase (MIOX), a key enzyme in the biosynthesis of glucaric acid. Using SDSPAGE and Western blotting, he was able to demonstrate conditions that enhanced the soluble
expression of MIOX. Interestingly, under certain cultivation conditions, he demonstrated the
expression of a truncated, insoluble version of MIOX which likely results in lower enzyme
activity and reduced glucaric acid production. This work will serve as the basis for the honors
thesis Drew plans to write and defend during his senior year.
Lactones of Glucaric Acid
In collaboration with Dr. Andy Evans, Paul Louigene explored the biological and chemical
production of the lactones that can be formed from glucaric acid produced by engineered strains
of E. coli. Using NMR, Paul provided presumptive evidence that lactone formation is enhanced
when the bacterial culture pH drops from an initial value of 7.0 to an end-of-fermentation value
of 5.5-6.0. Moreover, we suspect this is the 1,5-lactone form of glucaric acid and is formed
biologically as pH values of 5.5-6.0 are not adequate to catalyze the chemical formation of the
1,4-lactone, demonstrated in control reactions at pH 2 and heating at 90°C.
Renewable Fuels and Chemicals from Sugars Derived from Waste Cardboard
Avatar Sustainable Technologies (AST, Fayetteville, NY) is developing technology to extract
glucose, and to a lesser extent xylose, from waste cardboard. AST has kindly provided samples
of their waste sugar product to allow Drew students to demonstrate that these crude sugars can be
used to produce useful renewable fuels and chemicals.
Leslie Eyzaguirre-Mercado used a high ethanol-producing yeast from the American Type
Culture Collection (ATCC) to demonstrate that the waste sugar can be used to support ethanol
production. However, because the waste sugar has components that inhibit yeast growth and
metabolism, Leslie used an “adaptive evolution” technique to generate a new strain, from the
original ATCC strain, that can tolerate these inhibitory components and convert all the waste
sugar to ethanol.
Sara Silvestri used the same waste sugar sample to demonstrate the production of glucaric acid
using engineered E. coli cultures provided by Prof. Kristala Prather (MIT, Chemical
Engineering). To counter-act the toxicity of the sugar sample, Sara first grew the bacteria on
pure glycerol or xylose and then added the waste sugar for the conversion of the glucose to
glucaric acid.
Structural Analogues of the Antibiotic Teixobactin
Teixobactin is a non-ribosomal peptide antibiotic produced by the bacteria Eleftheria terrae and
recently discovered by Novobiotic Pharmaceuticals (Cambridge, MA). In this new collaboration
with Novobiotic, Erin Connors is exploring directed biosynthesis and the use of
methyltransferase reaction inhibitors to generate structural analogues of teixobactin that could
have better pharmacokinetic/pharmacodynamics properties. Initial results on the generation of
analogues using methyltransferase reaction inhibitors are encouraging. Novobiotic is generously
providing student stipend support, research materials, and lab protocols.
Honors 202 Seminar Course
Once again, I participated in the RISE seminar course (Honors 202) run by Prof. Alan Rosan
(Chemistry). I presented an initial overview of my research interests and then had the pleasure
of mentoring two very talented Freshman students. Josephine Emanuelli explored the prevalence
of hydrocarbon-degrading bacteria found in the Gulf of Mexico after the Deep Water Horizon oil
spill of 2012 and proposed the notion that these bacteria could be cultivated and kept “at the
ready” and deployed in the event of another oil spill disaster. Alexandra Koeck used Life Cycle
Assessment (LCA) and the principles of “greenwashing" to determine that the K-cup coffee
system (Green Mountain Coffee) is not as environmentally friendly as the manufacturer claims.
OTHER DREW-RELATED ACTIVITIES:
•
Arranged the donation of a new refractive index (RI) detector from Kalion Inc. This RI
detector has been installed on one of the Agilent 1100 HPLC systems and can support all
projects requiring the quantitation of sugars or other non-UV absorbable analytes
•
Worked closely with Drew University Facilities (Barry O’Connor and Jay Jackson) to
establish a “soft water” supply to the autoclave in HS 320 in hopes of extending the life of
this aging unit.
•
Continue to work closely with all members of RISE to ensure the smooth functioning of the
RISE/Biology lab, assisting all students as required.
NAME: Bimal DasMahapatra
Ph.D. 1977, Bio Chemistry, University of Calcutta, India
Post-Doctoral Research Fellow, Medical College of Wisconsin, Milwaukee, 1979-1981
Project Associate, University of Wisconsin, Madison, WI, 1981-1985
Senior Scientist, Schering-Plough Research Institute, Kenilworth, NJ, 1985 &
Retired as Research Fellow in 2008
Director, Oncoceutics Inc. 2009- 2013.
Fellow, RISE, September 2011-Presenrt
AREAS OF EXPERTISE AND RESEARCH INTERESTS:
Drug discovery research (pre-clinical) in Oncology and Virology. Evaluation and validation of
biological targets for disease, assay developments, identification of lead molecules and their
characterization for pre-clinical development. Current research interest is in restoration of tumor
suppressor activity in mutant p53 by small molecules for potential cancer therapy.
RESEARCH AND MENTORING ACTIVITIES AT RISE, DREW U.
Here at the RISE laboratory, my students are familiarized in pre-clinical drug discovery research
in oncology. In particular, they are trained in understanding biological targets in cancer,
developing assays which they use to screen and evaluate compounds affecting the target activity.
The research project they are working on is “Reactivation of mutant p53 by small molecules for
potential cancer therapy”.
The tumor suppressor protein p53, also known as the “Guardian of Genome” functions to
maintain genomic integrity and thus prevents carcinogenesis. p53, however, is inactivated in
almost all human cancers, and in 50% of cancer the protein is inactivated due to mutations in the
DNA-binding domain. These oncogenic mutations induce conformational change with reduced
stability of the protein in physiological temperature. Recently small molecules have been
discovered and are reported to bind the protein and restore transcriptional activity in mutant p53.
Although these molecules provide the proof of concept in reactivation of mutant p53, the
potency and therapeutic index of these molecules are inadequate for developing into
anti-cancer agents. My students in collaboration with Dr. Ron Doll’s group are exploring and
evaluating different classes of small molecules to identify novel compounds that will reactivate
mutant p53 with improved cell potency and safety.
Specifically, my students have developed various cell- based assays to measure restoration of
transcriptional activity of mutant p53 by small molecules. Once mutant p53 is reactivated, it
induces transcription of many genes, including p21 which is involved in growth inhibition.
Cancer cells carrying mutant p53 are treated with compounds and p21 expression is followed at
both mRNA and at protein level via PCR-based and western blot based assays. In addition, a
tumor cell growth inhibition assay has also been developed for evaluation of selectivity and
therapeutic index of these small molecules. The students learn how to grow mammalian cells and
maintain them for various experiments, gel electrophoresis, RT-PCR, and other biochemical
techniques. Several small molecules have been identified that induce p21 expression in tumor
cells with mutant p53, suggesting that these molecules can reactivate mutant p53. Students will
evaluate potency, toxicity of these molecules and continue to screen new molecules for improved
lead molecules.
I have mentored Ms. Jessica Shannon and Mr. Jhon Orozco during the summer of 2015 DSSI
program. Both have learned cell culture and western blot assay. Jessica did well in maintaining
various cell lines and was able to use them in p21 western blot assay.
In addition to Jessica and Jhon, I also mentored a high school student, Mr. Sapan Gupta from
Randolph High School. During the fall semester, Mr. Austin Larocca, Ms. Madeline Spiess and
Miss Victoria Farrell joined in the laboratory. They continue to work in the fall semester of 2015
and spring semester of 2016. They are all trained in cell culture, molecular biology techniques
and they carried out experiments to screen and characterize small molecules reactivating mutant
p53. Austin was awarded the ICFNJ (Independent College Fund in New Jersey) Scholarship for
his research work. Austin continues to work in the laboratory for fulfillment of his Honors
Research Thesis.
Mr. Tyler Dority of RISE Honors Seminar class of 2015, whom I mentored, published his
research report on Cancer Immunotherapy in The Drew Review, College of Liberal Arts, Vol, 9,
May 2016.
OTHER DREW-RELATED ACTIVITIES:
Continue to maintain tissue culture laboratory.
NAME: Arnold L. Demain
Ph.D. 1954, University of California at Berkeley, Microbiology
Merck & Co., Inc., 1954 – 1969
MIT: Professor of M.I.T. Nutrition and Food Science Dept. and Biology Dept., 1969 - 2001.
Research Fellow in Microbial Biochemistry at RISE: 2001 – present
AREAS OF EXPERTISE AND RESEARCH INTERESTS:
Microbial biochemistry, antibiotics, enzymes, fermentation, biofuels
RESEARCH PROJECTS AND MENTORING ACTIVITIES:
Supervised the research of Drew students Amreen Patel, Gulaba Khan, and Victoria Korn during
summer 2015 on production of the antibiotics platensimycin by Streptomyces platensis. During
fall of 2015, supervised research of Drew students Victoria Korn, Amreen Patel, Klarissa Jones
and Gulaba Kahn. During Spring 2016, supervised research of Victoria Korn, Krishnaben Patel,
Phadeline Evra and Klarissa Jones on the same subject. See research results below.
Professor Emeritus, M.I.T.
Member, National Academy of Sciences, USA
Member, National Academy of Sciences, Mexico
Member, National Academy of Sciences, Hungary
Fellow, American Academy of Microbiology (AAM)
Associate Editor, Applied Microbiology and Biotechnology
Member, Editorial Boards of 13 other journals
Fellow, Society for Industrial Microbiology
PUBLICATIONS in 2015 and 2016:
1.
A.L. Demain and S. Sanchez. The need for new antibiotics. In: Antibiotics: Current
Innovations and Future Prospects (S. Sanchez and A. L. Demain, Editors), pp. 65-82, Caister
Academic Press, Norfolk, UK (2015).
2.
P. Vaishnav, Y.J. Yoo, Y. J. Yoon and A.L. Demain. Immunosuppressants: remarkable
microbial products In: Bioactive Natural Products. Chemistry and Biology (G. Brahmachari,
Editor). Chapter 4, pp. 43-81, Wiley-VCH, Weinheim, 2015.
3.
A.L. Demain. To preserve human health, it is time to stop feeding antibiotics to farm
animals in the USA and other countries. (Editorial). Microbial & Biochemical Technology
7:e123. doi:10.4172/1948-5948.1000e123 (2015).
4.
C. Perkins, S. Siddiqui, M. Puri and A.L. Demain. Biotechnological applications of
microbial bioxconversions. Crit. Revs. Biotechnol. (2015).
5.
J. Spizek, K. Sigler, T. Rezanka and A.L. Demain. Biogenesis of antibiotics – viewing its
history and glimpses of the future. Folia Microbiol. DOI 10.1007/s12223-016-0462-y. 2016
Book published: Antibiotics: Current Innovations and Future Trends; Edited by Sergio Sanchez
and Arnold L. Demain. Caister Academic Press, Norfolk, U.K. 2015.
Book in press: Biotechnology of Microbial Enzymes: Production, Biocatalysis and Industrial
Applications; Edited by G. Brahmachari, Arnold L. Demain and Jose L. Adrio. Elsevier, 2016.
MEMBERSHIP IN PROFESSIONAL SOCIETIES:
American Society for Microbiology
Society for Industrial Microbiology & Biotechnology
American Chemical Society
Honorary Member, French Society of Microbiology
Honorary Member, Croatian Society of Biotechnology
R.I.S.E. RESEARCH RESULTS:
Earlier research by students had led to the successful development of a chemically-defined
medium, called PM7, for production of platensimycin by Streptomyces platensis. During 2015
and 2016, they established that a variant of production medium PM7, i.e., medium PM7A, was
an improved chemically-defined medium. The students also found that purines and pyrimidines
have no effect on platensimycin formation when added to medium PM7A. They then found that
one primary metabolite, i.e., L-aspartic acid, and the inorganic compound CaCO3 stimulate
formation of platensimycin in medium 7A, leading to the development of a new and improved
chemically-defined production medium called PM8. In this new medium, platensimycin
production was increased by addition of KCl.
RISE Annual Report, June 2016
NAME: Ronald J. Doll
Ph.D. 1975, Duke University, Organic Chemistry
Retired from Schering-Plough Research Institute/Merck Research Laboratories as Director of
Chemical Research, Oncology Chemistry, October 2010.
Tenure at RISE – October 2010 - present
AREAS OF EXPERTISE AND RESEARCH INTERESTS:
Synthetic organic chemistry, drug discovery of anti-cancer and CNS active compounds,
synthetic methods and preparing compounds with interesting biological, chemical and physical
properties.
RESEARCH PROJECTS AND MENTORING ACTIVITIES:
During the summer of 2015, six students worked in my lab for DSSI; Tayyaba Shakeel,
Ashley Alicea, Stephanie Sanchez, Amanda Robinson, Jed-Joan Edziah and Matthew Owen.
During the 2015 – 2016 school-years, I mentored six students in my laboratory. These students
were Tayyaba Shakeel, Stephanie Sanchez, Rebeccda Ferreira, Ian Pavalak, Vanessa Bagambe,
Andrew De Colle. We conducted drug discovery research in two therapeutic areas, oncology
and CNS diseases. In the oncology area we collaborate with RISE Fellow Dr. DasMahapatra
and his students who performed the tumor cell assays. In the CNS diseases project we have been
collaborating with scientists at Lundbeck Research USA and with Drew biology professor Dr.
Roger Knowles and his students. Both of these projects are described below.
I had two senior students that graduated in the spring of 2016. One was Stephanie
Sanchez, a transfer student from Venezuela, who graduated with an honors ACS accredited
degree in chemistry. Her honors thesis was entitled “Evaluation of Human Liver Metabolism of
Compounds that Reactivate Mutant p53 in Human Cancer Cells”. Stephanie is now in a Ph.D.
chemical engineering program at the University of South Carolina. My other graduating senior
was Rebecca Ferreira who also graduated with an ACS accredited degree in chemistry. She
presented her research and won 2nd place in the North Jersey ACS Section’s 68th annual
undergraduate research conference. Her presentation seminar was entitled “Synthesis of
Allosteric Stimulators of the Metabotropic mGluR4 Glutamate Receptor for Potential Therapies
of CNS Diseases”. Rebecca is now employed at Pfizer as a Bioanalytical Scientist. Her research
experience in quantitative LC/MS was instrumental in her getting the Pfizer job. During the
spring semester of 2016, I also mentored two students in the RISE Science Honors Seminar
Course.
OTHER DREW-RELATED ACTIVITIES:
I was a co-organizer of the Drew ResMed 2016 drug discovery course, and will
participate in planning the 2017 course. I also met with prospective Drew students and described
the science and research opportunities at Drew.
RISE - RELATED RESEARCH SUMMARY
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Drug discovery projects
All of the projects currently in my lab can now be considered true drug discovery
projects. Besides synthesizing new compounds for biological testing, my students also evaluate
our compounds in an in vitro human liver microsome metabolism assay, and determine if our
compounds can pass through GI tract and blood brain barrier membranes. These assays
determine the drug like properties of our compounds. Our goal is to optimize the potency,
selectivity and drug-like properties of our synthesized compounds. My students get a drug
discovery experience that is similar to scientists in the pharmaceutical industry.
Oncology - Reactivation of mutant p53 in human tumor cells
One of our research projects involves exploring compounds that reactivate mutant p53 in
human tumor cells as potential anti-tumor compounds. This stems from work that Dr.
DasMahapatra and I did at Schering-Plough concerning SCH 529074 and recently published, J.
Biol. Chem. (2010) 285, 10198-10212. We have two novel structural classes, as lead
compounds, the 2-aminobenzimidazole amide class and the quinoline carbamate class. A
compound in the first class was reported to bind to p53, but nothing was known about it
reactivating mutant p53 (US Patent 7,790,474 (2010)). Compounds in the second class were
reported to inhibit angiogenesis, by blocking the MetAP-2 protease. Since activated p53 also
inhibits angiogenesis, could these compounds also reactivate mutant p53. Our work at RISE
show that compounds in both of these structural classes do indeed reactivate mutant p53 in
human tumor cells. We are synthesizing compounds in both of these classes, with the goal to
optimize in-cell potency, selectivity and drug-like properties. My lab designs, prepares and
evaluates drug-like properties of the compounds, while Dr. DasMahapatra’s lab performs the
biological assays. My group have determined which of our compounds cross the blood brain
barrier and correlated this effect with structure and cLogP. My group has also evaluated the in
vitro human metabolic rate and identified metabolites of some of our compounds using human
liver microsomes. Using this data, we designed a compound with a metabolic rate similar to that
of marketed drugs.
CNS – Allosteric activation of the mGluR4 glutamate receptor
Central nervous system (CNS) diseases such as Parkinson’s and Alzheimer’s diseases
result in brain cell death due to over activation of ionotropic glutamate receptors. This process
raises intracellular Ca2+ concentration, resulting in cell death. There is evidence suggesting that
activation of metabotropic glutamate receptors activate feedback processes that reduce cell
activation, thus protecting these effected cell from cell death. Lundbeck Research USA
published on a cyclohexyl-cis-1,2-dicarboxamide, LuAF21934, that was an allosteric mGluR4
activator (Neuropharmacology 2013, 66, 160-169). We set up collaboration with Lundbeck
Research USA to prepare analogues of LuAF21934. Lundbeck would test our compounds in
their Parkinson’s disease assays. My students prepared six analogues, and resolved two of them
into single enantiomers. Unfortunately, Lundbeck Research USA closed down, so the
compounds were not tested in the Parkinson’s assays. However, we recently set up collaboration
with Dr. Roger Knowles, a professor in Drew’s Biology department. Dr. Knowles group is
testing our synthesized compounds in an Alzheimer’s disease cell survival assay. After testing
one of our compounds, the Knowles’ group showed positive cell protective activity. With this
encouraging data, we are preparing additional compounds in this structural class. We also
showed that all of our synthesized compounds cross the blood brain barrier, which is necessary
in treating CNS diseases. We also performed in vitro human metabolism studies on one of our
compounds and showed the metabolic rate was fast but reasonable for an exploratory structural
class. We plan to identify metabolites and design and prepare compounds that have improved
metabolic rates.
Publications:
Manuscripts and abstracts (2015-2016)
1. Discovery of Novel 3,3-Disubstituted Piperidines as Orally Bioavailable, Potent, and
Efficacious HDM2-p53 Inhibitors
Bogen, Stephane L.; Pan, Weidong; Gibeau, Craig R.; Lahue, Brian R.; Ma, Yao; Nair,
Latha G.; Seigel, Elise; Shipps, Gerald W.; Tian, Yuan; Wang, Yaolin; Doll, Ronald J. et
al,
Medicinal Chemistry Letters (2016), 7(3), 324-329.
2. Drug discovery research with undergraduate students: An excellent facilitator of
STEM education
Doll, Ronald J.
Abstracts of Papers, 250th ACS National Meeting & Exposition, Boston, MA,
United States, August 16-20, 2015 (2015), CHED-54
3. Discovery of novel chiral 3o-SMe pyrrolidine as extracellular regulated kinase
(ERK) inhibitors
Boga, Sobhana B.; Alhassan, Abdul-Basit; Cooper, Alan B.; Doll, Ronald; Shih, NengYang; Deng, Yongqi; Shipps, Gerald W.; Sun, Robert; Desai, Jagdish; Zhu, Hugh; et al
Abstracts of Papers, 251st ACS National Meeting & Exposition, San Diego, CA,
United States, March 13-17, 2016 (2016), MEDI-285.
MEMBERSHIP IN PROFESSIONAL SOCIETIES:
American Chemical Society
NAME: John R Eickmeyer
Ph.D. Cornell University 1976
Research Associate University of California and CERN, 1976-1980
Member of Technical Staff, Bell Laboratories, 1980 -2002
Retired as Distinguished Member of Technical Staff, General Dynamics Advanced Information
Systems, 2012
Rise Fellow since 2012
AREAS OF EXPERTISE AND RESEARCH INTERESTS:
Optics; Optical Communications; Fundamental Problems in Quantum Mechanics including
coherence, decoherence and the transition to classical physics.
RESEARCH PROJECTS AND MENTORING ACTIVITIES:
During the fall and spring semesters I mentored a student, Michael Clancy, for an independent
study. The study was to explore the ability to improve handover in wireless communications. In
wireless communications, handover occurs when one cell signal diminishes in link quality, and
another cell’s signal increases in link quality. This change in link quality occurs commonly when
the mobile device is moving. The study used a Kalman filter to predict a simulated time series of
the received signal power. The work involved constructing the simulation, creating and tuning
the Kalman filter. The performance of several filters were compared, each one consisting of a
minimum least square fit polynomial function to predict the future signal. Polynomials of degree
0-3 were used. The quadratic predictor (degree 2) was the most robust. The Kalman filter
represents an improvement over “batch process” filter used in last year’s study since it is capable
of providing continual updates to the best fit parameters requiring less computing time and
shorter delays.
This spring I also mentored two students for the Freshman Honors Seminar in Natural Science.
Malek Elsayyid worked with me to investigate Radiation Hormesis, the theory that very small
doses of radiation may actually stimulate gene repair mechanisms and help organisms recover
from larger doses administered later. This topic is, needless to say, not only controversial but
also an area of active research due to its implications for diagnostic and therapeutic uses of
radiation in medicine.
Andrew Wang looked at the use of thorium as a fuel in nuclear reactors. Thorium is a natural
radioactive element that is more plentiful than uranium. Its potential advantages for peaceful
uses include the shorter half lives of its decay products and the difficulty of using it in nuclear
weapons. While nuclear power research is languishing in the United States, India, which has
large natural stores of thorium, has a major program to develop a commercial thorium reactor.
This last academic year was the first year of operation for the new office/lab, which was featured
in the student physics newsletter, “The Dilated Times” The lab has enough space to house both
the QKD apparatus and a new fluorescence lifetime spectrometer. In the coming year I hope to
get the fluorescence apparatus operational and sponsor a student project using the equipment.
MEMBERSHIP IN PROFESSIONAL SOCIETIES:
Optical Society of America
American Association of Physics Teachers
Name: C. Anderson Evans, Fellow
Education
B.S. Chem 1968, Georgia Tech
Ph.D. 1974, University of Georgia, Organic Chemistry
Post Doctoral Experience
Centre d'Études Nucléaires, Grenoble, France
1973-74
ESR Studies, Free Radical Dynamics, with Prof. Andre Rassat
University of Western Ontario, London, Ontario
1974-76
ESR Studies, photosynthesis, micelles, with Professor James R. Bolton
Academic Experience
Part time faculty, Mathematics, Teaching Freshman Calculus, Georgia Tech, 1967-68
Adjunct, Drew University, 1978
Adjunct, Fairleigh Dickinson University, 1988-2002
RISE, Drew University, 2012 – present
Industrial Positions
Varian Associates, ESR Applications Chemist, 1976-80
JEOL (USA), Inc, Nuclear Magnetic Resonance (NMR) Applications Chemist, 1980-84
Berlex Laboratories, NMR Spectroscopist, 1984-87
Schering-Plough Research Institute, Fellow, 1987-2010
Merck Research Laboratories, Principal Scientist, 2010-11
-
Retired, 2011
Membership in Professional Societies
American Chemical Society
American Association for the Advancement of Science
International Society of Magnetic Resonance
Past Professional Activities
NMR Awards Committee, Eastern Analytical Symposium
Chair, North Jersey American Chemical Society NMR Discussion Group
Research Interests
Applications of Nuclear Magnetic Resonance (NMR)
Organic structure determination, intramolecular dynamics in organic molecules
Nuclear Overhauser Effect measurement of “exact” interproton distances
Use of detergent micelles to assess hydrophilic/hydrophobic interactions of potential drug
molecules
Theoretical calculation of NMR spectra using Density Matrix techniques
Pulse Sequence Development
Research Projects and Mentoring Activities
During 2015 - 2016, I provided NMR support for organic structure determination to RISE and/or
DSSI students Rebecca Ferreira, Matt Owen, Stephanie Sanchez, Ashley Alica, Tayyaba
Shakeel, Amanda Robinson, Ian Pavlak, Vanessa Bagambie, Andrew DeColle, and Ian Nadler
(Dr. Doll). For Dr. Gullo I provided NMR support to RISE and/or DSSI students Doug Molina,
Bishoy Awadalla, Erin Connors, Dalia Lima, Giuseppe Birnal, and Christian Lisandro. I also
helped students carrying out research mentored by Drew Faculty. These were Dani Leviss and
Delmis Hernandez (Dr. Hinrichs), and Robert Sommerhalter (Dr. Pearsall). I collaborated with
Dr. Connors to mentor Paul Louigene's project which used 13C NMR to follow the production of
glucaric acid by genetically modified E. Coli. Glucaric acid is a "green" substitute for petroleum
based starting materials for large scale industrial synthesis of chemical intermediates. Stephanie
Sanchez wanted to do an NMR laboratory project in Dr. Hinrichs' Physical Chemistry class. I
suggested a dynamic NMR project to follow the hindered rotation of dimethylbenzamide in
DMSO-d6 as a function of temperature. The project was successful, producing the same value of
the energy of activation as reported in the literature. I attended Stephanie's well received in-class
presentation of the project.
In Spring Semester 2016 I mentored Darci Gautam, Meghan McDermott, and Molly Murphy in
Honors 202 (RISE Honors Symposium). All three students used the literature to research the
application of fMRI (functional MRI) to determine the regions of the brain involved in their
subject of interest. Darci developed a paper entitled "Self-injury and Pain: Non-suicidal Selfinjury and the Effects it has on the Neurological Processing of Pain". Meghan's topic was "An
Analysis of the Effect of Exercise on the Aging Brain". Molly investigated "The Use and
Misuse of Antipsychotic Medication in the Treatment of Schizophrenia".
Other Drew Activities
I am a member of the committee planning the celebration of the 35th anniversary of the founding
of RISE.
NAME: Vincent P. Gullo
Ph.D. 1975, Columbia University, Organic Chemistry
Merck Research Laboratories – Research Fellow 1975 - 1983
Retired from Schering-Plough Research Institute as Senior Director 1983 – 2004.
Vice President of Drug Discovery, Cetek Corporation 2004 - 2006
Tenure at RISE - April 2007 - present
AREAS OF EXPERTISE AND RESEARCH INTERESTS:
Drug discovery, natural products, high throughput screening and medicinal chemistry
RESEARCH PROJECTS AND MENTORING ACTIVITIES:
During the summer 2015, I supervised the research of Christian Lisandro (sophomore), Douglas
Molina (junior) and Erin Connors (freshman) in the DSSI program. Bishoy Awadalla (senior)
and Giuseppe Bernal (senior) worked in my lab for research credits during the Fall 2015 and
Spring 2016. All the students in my laboratory, except Christian Lisandro, are working on the
synthesis of new antibacterial compounds discovered here at Drew. Christian is working on
synthesizing analogs of a novel antibiotic, teixobactin, discovered at Novobiotic
Pharmaceuticals.
During the Spring semester 2015, I mentored two students, David Van Dongen and Jordan
Burnett in the RISE Honors course.
OTHER DREW-RELATED ACTIVITIES:
Co-chairman of the organizing committee for the Residential School on Medicinal Chemistry &
Biology in Drug Discovery
OTHER PROFESSIONAL ACTIVITIES:
Member of the American Chemical Society Awards Committee for the Nakanishi Prize
Biotechnology/pharmaceutical consultant in high throughput screening, natural products and
preclinical lead compound optimization
MEMBERSHIP IN PROFESSIONAL SOCIETIES:
American Chemical Society
Society for Industrial Microbiology & Biotechnology
Theobald Smith Society
ADDENDUM: RESEARCH RESULTS
With increasing microbial resistance to current antibiotics, commonly referred to as the
“antibiotic crisis”, there is an urgent need to discover new antibiotics to control these resistant
strains. The overall objective of our research project is to discover novel antibacterial compounds
and optimize the activity by synthesizing analogs. The project initially involved the testing of
several hundred compounds from a synthetic library, prepared at Drew University by Dr.
William Houlihan, for antibacterial activity against a gram-positive organism, Bacillus subtilis.
We chose this microorganism because it serves as a model for other gram-positive organisms, for
example, MRSA (methicillin-resistant Staphylococcus aureus). Compounds with antibacterial
activity were discovered and a compound series with significant antibacterial activity was
selected for synthetic optimization by the preparation of analogs.
During 2015 the students have successfully worked out all the methods and conditions for five of
the six steps required to synthesize analogs. Conditions are being developed and finalized for the
sixth and final step. Two analogs have been synthesized on a small scale.
In addition, a new antibacterial project has started with Novobiotic, a biotech company.
Novobiotic reported in Nature an exciting new antibiotic, teixobactin, with potent antibacterial
activity. Since I am a consultant for Novobiotic, I was able to negotiate an arrangement where I
will perform some chemical modifications in the laboratory at Drew with a student, Christian
Lisandro. The objective of this project will be to understand the chemical features of the
molecule required for antibacterial activity and to seek to improve the compound’s
pharmacokinetic properties. Christian successfully added a glycine to teixobactin working with
small amounts of teixobactin. This is being scaled up this summer (2016). He also successfully
added a protecting group to teixobactin which is necessary for future analog synthesis.
A second project was initiated with Novobiotic in collaboration with Dr. Connors. This project
involves the modification of teixobactin using a microbiological approach. Work is underway
this summer (2016) with a student, Erin Connors. Both students, Erin and Christian, are
supported by Novobiotic for DSSI.
NAME: Jon Kettenring
Ph.D. 1969, University of North Carolina, Statistics
Retired from Telcordia Technologies (formerly Bellcore) as Executive Director, 2003;
Member of
Technical Staff, Bell Laboratories, 1969-1984
RISE Fellow: 2004 – present; Director June 2008 – present
· AREAS OF EXPERTISE AND RESEARCH INTERESTS:
Applied statistics, multivariate statistical methods, robust statistical methods, statistical
graphics, data analysis, data mining, cluster analysis, and analysis of massive datasets
•
STUDENT PROJECTS AND MENTORING ACTIVITIES:
o Richa Patel, Mathematics and Economics double major, junior—mentored her
independent study project on multivariate statistics, 4 credits, fall semester
o Liz Pemberton, Physics major, Mathematics minor, senior—mentored her
independent study project on multivariate statistics, 4 credits, fall semester
o Kyra Cipolla, freshman—mentored her Honors 202 project on coral reefs
o Zarina Akbary, freshman—mentored her Honors 202 project on cross-media
metrics
o Kamila Wszola, Mathematics major, senior—mentored her independent study
project on multiple regression analysis, 3 credits, spring semester
•
OTHER DREW-RELATED ACTIVITIES:
o Public Health Advisory Committee
o RISE Talks Series: with Minjoon Kouh organized talks by internal and external
speakers
•
PUBLICATIONS AND TALKS:
o Panel speaker on “implicit bias” at Joint Statistical Meetings in Seattle, August 9,
2015
o Golbeck, A.L., Ash, A., Gray, M., Gumpertz, M., Jewell, N.P., Kettenring, J.R.,
Singer, J.D., and Gel, Y.R. “A conversation about implicit bias”, Statistical Journal of
the IAOS, to appear.
o Kettenring, J. R. (2016), Discussion of paper by Cristiano Varin, Manuela Cattelan,
and David Firth, Statistical modeling of citation exchange between statistics journals,
Journal of the Royal Statistical Society, Series A, 52, 54.
o RISE Talk on “Citation Data Analysis” 4/13/16
•
OTHER PROFESSIONAL ACTIVITIES:
o Member, Advisory Board of Center for Discrete Mathematics and Theoretical
Computer Science (DIMACS), housed at Rutgers University. (DIMACS is a
partnership of six local universities and companies)
o Member, Advisory Board for the Command, Control, and Interoperability Center for
Advanced Data Analysis, a Department of Homeland Security Center of Excellence,
based at DIMACS
· MEMBERSHIPS IN PROFESSIONAL SOCIETIES:
o Fellow, American Statistical Association
o Elected Member, International Statistical Institute
o Fellow, American Association for the Advancement of Science