1. health and fitness
2. disease

INVITATION LETTER
Following the success of prior conferences, Korean American Society in Biotech and
Pharmaceuticals (KASBP) cordially invites all members and friends to the 2014 KASBP Fall
Symposium, hosted by KASBP, Daewoong Pharmaceutical Co. Ltd., and Green Cross Co., and
sponsored by KHIDI, KSEA, and KUSCO. The topics of this symposium are focused on general
issues in drug discovery and development with the following formats to share experiences and
expertise of the speakers with the attendees and among the attendees.
a. Forum A
Recent trend in oncology drug discovery, cell therapy, pre-formulation and rare disease
drug development presented by the scientists in Pharmaceutical R & D and Non-profit
research Organization
b. Forum B
New topics related to Marketing and regulatory topics such as QbD (Quality by Design)
application, and antifungal and antibacterial drug development
c. Round Table Discussion
Small group discussion between researchers in academia and industry to understand the
drug R&D and approval processes in the pharmaceutical industry
d. Job Fair
An open job fair for attendees to have a chance to meet the hiring managers and
representatives from Korean pharmaceutical companies or life science research institutes
This symposium will focus on current trends in drug discovery and highlighting
professionals in biotech and pharmaceutical industries. This year, the symposium has
successfully recruited outstanding speakers and panels to cover the topics described above.
Additionally, a distinguished Korean-American scientist Kinam Park, Ph.D. (Purdue University)
will be awarded with KASBP-Daewoong Achievement Award based on his contribution to drug
discovery and development. He will give a keynote speech with a title, “More than I thought I
could be” during the symposium. The symposium also offers a round table discussion with
pharmaceutical industry and academia professions to provide valuable career development tips
to young scientists.
One of the meaningful events is presenting the KASBP-Daewoong and KASBP-Green Cross
fellowship awards to young scholars such as graduate students and post-docs who exhibit
excellence in research. This symposium will provide an opportunity for members to establish
professional networks, and share information and experiences amongst members in pursuit of
excellence in research and development.
2014 KASBP Fall Symposium Organizing Committee
SYMPOSIUM SCHEDULE AT A GLANCE
November 7, 2014, Friday
03:00 pm –
05:30 pm – 06:30 pm
06:30 pm – 06:50 pm
06:50 pm – 07:30 pm
07:30 pm – 07:40 pm
07:40 pm – 08:40 pm
08:40 pm – 09:00 pm
09:00 pm – 09:20 pm
09:20 pm – 10:20 pm
Job Fair / Exhibition
Registration
Opening and Congratulatory Remarks
Dinner
Award Ceremony
Keynote Speech
Sponsor Talk 1: Daewoong
Sponsor Talk 2: Green Cross
Round Table Discussion A (Pharma industry - Academia)
November 8, 2014, Saturday
07:00 am – 08:30 am
08:00 am – 09:00 am
08:50 am – 09:00 am
09:00 am – 10:10 am
10:10 am – 10:25 am
10:25 am – 10:45 am
10:45 am – 11:55 am
11:55 am – 12:30 pm
12:30 pm – 02:45 pm
02:45 pm – 03:00 pm
03:00 pm – 03:40 pm
03:40 pm – 04:00 pm
04:00 pm – 05:10 pm
05:10 pm – 05:30 pm
06:00 pm – 08:30 pm
Round Table Discussion B
(Regulatory Perspectives in Drug Approval Process)
Registration & Light Breakfast
Opening Remarks
Forum A1 Presentation
Sponsor Talk 3: KSEA
Coffee Break
Forum A2 Presentation
Award Presentation – Six Oral Presentations by Fellowship awardees
Photo time, Lunch, & Poster Viewing
Sponsor Talk 4: KUSCO
Forum B1 Presentation (Panel discussion)
Coffee Break
Forum B2 Presentation
Closing Remarks
Dinner & Networking
2
SYMPOSIUM SCHEDULE IN DETAIL
November 7, 2014 (Friday)
Job Fair & Exhibition 3:00 pm ~
Coordinator: Sahee Kim (RevHealth, LLC), Dongweon Song (Novartis)
Registration & Reception Cocktail
5:30 pm ~ 6:30 pm
Coordinators: Jun Hyuk Heo (Merck), Alex Kim (Merck), Dahea You (Rutgers University)
Opening & Congratulatory Remarks and Dinner
6:30 pm ~ 7:30 pm
Coordinator: KASBP President-Designated: Jae Uk Jeong, GSK
Opening Remarks
KASBP President: Youngsun Kim, VaxInnate
Congratulatory Remarks
Daewoong Pharmaceutical Co.: President, Jong-Wook Lee
Green Cross Corp.: Executive Vice President, Eun Chul Huh
KHIDI USA: General Director, Jung-hoon Woo
Award Ceremony
7:30 pm ~ 7:40 pm
KASBP-Daewoong Achievement Award
Keynote Speech
7:40 pm ~ 8:40 pm
Award Lecture (KASBP-Daewoong Achievement Awardee 2014)
“From Pills to Nanoparticles: The 10X Progress in Drug Delivery Research”
Kinam Park, Purdue University
Sponsor Talk
8:40 pm ~ 9:20 pm
Daewoong: “Daewoong's Global Strategy”
Sang Ho Lee, Head of New Drug Development Lab.
Green Cross: “Global project and R&D pipeline of Green Cross”
Young-Seoub Park, Deputy General Manager, Research Planning Team
Round Table Discussion A
9:20 pm ~ 10:20 pm
Pharma industry – Academia, and Career Development
Chair: Chang-Sun Lee, PTC Therapeutics
Networking
9:20 pm ~ 11:45 pm
3
November 8, 2014 (Saturday)
Round Table Discussion B
7:00 am ~ 8:30 am
Regulatory Perspectives in Drug Approval Process
Chair: Yun H. Choe, Lucas & Mercanti, LLP
Registration & Breakfast
8:00 am ~ 9:00 am
Coordinators: Jun Hyuk Heo (Merck), Alex Kim (Merck),
Dahea You (Rutgers University)
Opening Remarks
8:50 am ~ 9:00 am
Program Chair: K. Stephen Suh, Hackensack University Medical Center
Forum A1------Chair: KASBP-Boston President, Sean Kim, Novartis
9:00 am ~ 10:10 am
“Selectivity Challenge in Kinase Drug Discovery”
Mooje Sung, Novartis
“Immunotherapies for Cancer”
Byoung Ryu, Bluebird Bio
Sponsor Talk
10:10 pm ~ 10:25 am
KSEA: “Introduction to KSEA”
Sung Yi, Executive Director of KSEA; Portland State University
Coffee Break
10:25 am ~ 10:45 am
Forum A2------Chair: KASBP-Phila President, Younghwan Jin, GSK
10:45 am ~ 11:55 am
“Acceleration Drug Discovery and Advancing Knowledge in Huntington Disease”
Larry C. Park, CHDI Foundation
“Role of Preformulation on Biopharmaceutical Evaluation”
Hyungchul Kim, Astra Zeneca
Award Presentation-------Chair: Eunsung Junn, Rutgers University
11:55 am ~ 12:30 pm
KASBP-Green Cross and KASBP-Daewoong Fellowship Award Ceremony
Oral Presentations by Fellowship Awardees
4
12:30 pm ~ 2:45 pm
Photo time, Lunch & Poster
Poster Presentation-------Chair: Eunsung Junn, Rutgers University
Sponsor Talk and Forum B1---Chair: KASBP-Connecticut President, Seungwon Chung, Pfizer
2:45 pm ~ 3:00 pm
Sponsor Talk
KUSCO: “Introduction to KUSCO”
Kiho Moon, Director
Business and Market Assessment (Panel discussion)
3:00 pm ~ 3:40 pm
“Global Pharm Market Today”
Moderator: Eun-Ju Ryu, Pfizer
Panelists: Jinhee Park (Novartis), Bokyung M. Kim (Merck),
Coffee Break
3:40 pm ~ 4:00 pm
Forum B2 -------Chair: KASBP-DC Vice-President, Sang Tae Park, Macrogen Clinical Lab.
4:00 pm ~ 5:10 pm
“Design space building for control of critical quality attributes of a model monoclonal
antibody”
Seongkyu Yoon, University of Massachusetts Lowell
“Role of Clinical Pharmacology in Antimicrobial and Antifungal Drug Development”
Seong Hoon Jang, Pharmacologist
Closing Remarks
5:10 pm ~ 5:30 pm
KASBP President: Youngsun Kim, VaxInnate
Dinner & Networking
6:00 pm ~ 8:30 pm
Minado Restaurant (Tel. 973-734-4900)
2888 New Jersey 10, Morris Plain, NJ 07950
5
KASBP-DAEWONG AWARDEE LECTURE
From Pills to Nanoparticles: The 10X Progress in Drug Delivery Research
Kinam Park, Purdue University, Departments of Biomedical Engineering & Pharmaceutics
Drug delivery systems are designed to deliver drugs in efficient
ways to maximize the efficacy of the drugs and to increase the
patients’ compliance. The history of drug delivery technologies
spans only 60 years, and during that time numerous new drug
delivery systems have been developed, and hundreds of
advanced formulations have been marketed. Over the years,
significant advances have been made, and the formulation was
improved from simple aspirin pills to the state-of-the-art
nanoparticle technologies. While the progresses made during
the last 60 years have been exciting, more breakthrough
technologies are required to treat patients with various diseases, such as cancers and diabetes.
The next 10X advances in drug delivery requires thinking in new boxes. This talk describes
history of drug delivery through the experience of one drug delivery scientist.
2006-present
Showalter Distinguished
Professor
2005-present
Editor-in-Chief
Journal of Controlled Release
2001-present
President
Akina, Inc.
1998-present
Professor
Biomedical
Engineering
Purdue University
1994-present
Professor
Pharmaceutics
Purdue University
1990-1994
Associate Professor
Pharmaceutics
Purdue University
1986-1990
Assistant Professor
Pharmaceutics
Purdue University
1983-1985
Postdoc
Chemical
Engineering
University of WisconsinMadison
1979-1983
Ph.D.
Pharmaceutics
University of WisconsinMadison
1975-1977
Lieutenant
R.O.T.C.
Korean Army
1971-1975
B.S.
Pharmacy
Seoul National University
Biomedical
Engineering
6
Purdue University
ABSTRACT
From Pills to Nanoparticles: The 10X Progress in Drug Delivery Research
Kinam Park, Purdue University, Departments of Biomedical Engineering & Pharmaceutics
Drug delivery systems are designed to deliver drugs in efficient ways to maximize the efficacy of
the drugs and to increase the patients’ compliance. The history of drug delivery technologies
spans only 60 years, and during that time numerous new drug delivery systems have been
developed, and hundreds of advanced formulations have been marketed. Over the years,
significant advances have been made, and the formulation was improved from simple aspirin
pills to the state-of-the-art nanoparticle technologies. While the progresses made during the last
60 years have been exciting, more breakthrough technologies are required to treat patients with
various diseases, such as cancers and diabetes. The next 10X advances in drug delivery requires
thinking in new boxes. This talk describes history of drug delivery through the experience of
one drug delivery scientist.
Selectivity Challenge in Kinase Drug Discovery
Mooje Sung, Novartis
Cancer is characterized by uncontrolled cellular proliferation. The passage of cells through the
cell cycle occurs through discrete phases controlled by cyclins which appear and disappear with a
defined periodicity, in association with their Cyclin-Dependent Kinase partners. The classical
model of mammalian cell cycle, which has originated from pioneering studies of yeast genetics by
Paul Nurse et al, places specific cyclin-CDK pairs at key transition points. The model does not
differentiate between normal or abnormally dividing cells, nor does it differentiate between tissue
or cell types. Early attempts to target CDKs led to pan inhibitors and difficulty separating
cytotoxicity from efficacy. Recent progress in the understanding of the role of CDKs in the cell
cycle control demonstrated that abolishing CDK4/6 kinase activity and subsequent reactivation
of Rb in tumors inhibited tumor and growth. Therefore, a pharmacological approach to inhibition
of cyclin-dependent kinases 4 and 6 (CDK4/6) using highly selective small molecule inhibitors
has the potential to provide novel cancer therapies for clinical use. Achieving high levels of
selectivity for CDK4/6, versus other ATP-dependent kinases, presents a significant challenge.
Herein, we describe several approaches in parallel toward identifying potent and highly selective
inhibitors of both CDK4 and CDK6 with the appropriate profile.
7
Immunotherapies for Cancer
Byoung Ryu, Bluebird Bio
Cancer is the second leading cause of death in the US. To treat advanced cancers, various forms
of immunotherapies have been developed, which include immune check point inhibitors,
antibody therapies and adoptive cell therapies. A brief overview of current immunotherapies
will be presented. In particular, chimeric antigen receptor (CAR) modified T cell therapy will be
discussed in details. In the CAR-T therapy, patients’ own peripheral T cells are isolated,
engineered to express cancer targeting cell surface receptor, and the modified T-Cells are infused
back to patients. The CAR expressing T-cells are able to kill tumor cells in vivo resulting in
disease free or reduced tumor load. Most recent clinical trials using CAR-T cell against CD19
antigen have shown remarkable complete response rate (up to ~90% in cumulative data) in
refractory acute lymphoblastic leukemia patients. Potential toxicity, strategies to mitigate the
toxicity, and key players in CAR-T immunotherapy will be also discussed at the end.
Acceleration Drug Discovery and Advancing Knowledge in Huntington Disease
Larry C Park, In Vivo Research, CHDI Foundation, Inc
CHDI Foundation is a privately-funded, not-for-profit biomedical research organization devoted
to a single disease – Huntington’s disease (HD). Our mission is to develop drugs that will slow
the progression of HD and provide meaningful clinical benefit to patients as quickly as possible.
To achieve this CHDI manages a diverse portfolio of research projects through a novel virtual
model that encourages scientific collaboration to more directly connect academic research, drug
discovery and clinical development. Our activities extend from exploratory biology to the
identification and validation of therapeutic targets, and from drug discovery and development to
clinical studies and trials. We work closely with a network of more than 600 researchers in
academic and industrial laboratories around the world in the pursuit of these novel therapies,
providing strategic scientific direction and management to ensure that our common goals remain
in focus. We’ve recently had some notable progress in this regard; an anti-sense oligonucleotide
therapeutic approach that CHDI helped develop with ISIS Pharmaceuticals was recently the
subject of substantial investment from the pharmaceutical company Roche, and we are currently
working with Pfizer to evaluate their phosphodiesterase 10 inhibitor in humans. As a not-forprofit entity we have no competitors, and our bottom line is ensuring the shortest possible time to
getting effective therapeutics to HD patients. As such, a big part of CHDI’s remit is to
collaboratively enable any researcher that is interested in working on HD by lowering the barrier
to entry through the provision of HD domain knowledge, reagents, protocols, animal models or
funding. In our role as a collaborative enabler, CHDI seeks to bring the right partners together to
identify and address critical scientific issues to increase the understanding of HD and hasten the
development of therapeutic approaches to clinical evaluation as rapidly as possible.
8
Role of preformulation on Biopharmaceutical Evaluation
Hyungchul Kim, Astra Zeneca
The preformulation is the first step of activities to design an optimum drug delivery system of
drug candidates which involves multiple skill areas such as solid state, formulation, analytical
and biopharmaceutics. The goals of preformulation are to characterize the physicochemical
properties of drug substances and understand the fundamental variables and their relationship of
performance. Developability report of drug candidates provides risk assessment, mitigation plan,
and clinical formulation strategy as early as possible to reduce expenditure in the development
process. The role of preformulation during drug discovery and early development stage will be
described and the impact of a thorough understanding physical form on a pre(clinical)
formulation development and role of in silico simulation tool will be presented through case
studies.
Global Pharm Market Today: Panel Discussion
Eun-Ju Ryu, Pfizer (Moderator)
Jinhee Park, Novartis
Bokyung Michelle Kim, Merck
The global pharmaceuticals market is worth US$300 billion, and expected to increase to US$400
billion by 2016. As the market continues to expand, traditional mass marketing and block buster
approach are no longer valid to capture the benefit of this rapid growth, but target market
approach with innovative value added service marketing become increasingly critical for the
business success. As the market moves quickly towards high price/small volume specialty
drugs, how to maximize patient access to the new drugs while maintaining optimal pricing is one
of the key questions we need to ask in today’s marketing as well as selection of target
development programs.
We hope to cover some major changes in global marketing and market access perspectives during
this session. We also briefly discuss ‘license-in/out’ opportunities from the business development
and commercialization perspective since this links to a larger business question, ‘what is the
added value from this deal?’
9
Design space building for control of critical quality attributes
Of a model monoclonal antibody
Seongkyu Yoon, Department of Chemical Engineering, University of Massachusetts Lowell
Quality by design is an innovative approach introduced by FDA, which ensures the quality of the
product by maintaining tight quality standards. According to ICH Q8 “Quality cannot be tested
into product i.e. Quality should be build in by design”. Exploration of design space can set the
control guidelines for process objectives such as titer and product quality. Herein, we used
experimental design approach to study eleven process variables in monoclonal antibody
production. It was found that engineering changes significantly impact the glycan profiles of the
monoclonal antibodies. Regression models were built for Critical quality attributes (CQA),
Integrated Viable Cell Density (IVCD) and producttiter. Design space was explored using Monte
Carlo simulation. Optimum operating conditions and CQA specifications were determined by
exploration of design space. Current study indicates that specifying the optimum
operatingconditions can reduce risk of failure.
Keywords: Design of experiments (DoE), Monoclonal Antibody, Quality by Design (QbD),
Glycan Profiling, Critical quality attributes (CQA), Integrated Viable Cell Density (IVCD).
Unmet Medical Needs, Challenges, and Role of Clinical Pharmacology in Antibacterial and
Antifungal Drug Development
Seong Hoon Jang, Pharmacologist
There are continuous and urgent unmet medical needs for new antibacterial and antifungal drugs
for the treatment of patients infected with pathogenic microbes resistant to currently available
drugs. However, antibacterial and antifungal drug development has been declined because of
many reasons including economic issues, the inherent challenges of studying a therapeutic for
infectious disease, and scientific issues related with clinical trial designs. Several activities and
initiatives to facilitate the development of new antibacterial and antifungal drugs have been
undertaken by public agencies including the FDA, the NIH, and the CDC. These activities and
initiatives include establishing (a) streamlined clinical trial design to evaluate the efficacy of
antibacterial and antifungal drugs against drug-resistant pathogenic microbes, (b) biomarkers for
adequate efficacy endpoints and rapid diagnostics of antibacterial/antifungal susceptibility, and
(c) incentives to encourage antibacterial and antifungal drug development. In presentation,
current challenges and future considerations in antibacterial and antifungal drug development
will be discussed. In addition, it will also be discussed how to apply animal and/or patient
PK/PD data to support clinical efficacy of antibacterial and antifungal drugs as well as to select
clinically effective doses.
The opinions and information in this presentation are mine, and do not represent the views and/or policies
of the U.S. Food and Drug Administration.
10
2014 FALL KASBP FELLOWSHIP RECIPIENTS
SWI/SNF-mutant cancers depend upon non-catalytic activity of EZH2
Kimberly H. Kim,, Dana-Farber Cancer Institute, Dept, of Pediatric Oncology, Harvard University
Inactivating mutations in the subunits of SWI/SNF ATP dependent chromatin remodeling
complex has been associated with malignant transformation of both pediatric and adult cancers
indicating that the SWI/SNF complex functions as major tumor suppressors. Over the past 18
months, recent human genetic screen revealed that the subunits of the SWI/SNF complex are
specifically inactivated in various types of cancers including lung, breast, bladder, endometrial,
ovarian, and more cancers. Additionally, mouse modeling experiments demonstrate profound
tumor formation following Snf5 inactivation. Mechanistically, we have shown that the
inactivation of SNF5 caused elevated expression of EZH2, a subunit of Polycomb complexes, and
that Polycomb target genes were repressed with increased level of H3K27-trimethylation in SNF5deficient fibroblasts and cancers. While these data have established a significant reversal
relationship between the SWI/SNF and Polycomb complexes in regulating growth and
preventing oncogenic transformation, the reason why each subunit is associated with distinct
cancer spectra and whether similar antagonism between two epigenetic regulators present in the
wide spectrum of cancers containing inactivating mutations in subunits of the SWI/SNF complex
are largely unknown.
Interestingly, recent studies support the concept that imbalanced epigenetic antagonism between
SWI/SNF chromatin remodelers and Polycomb cause disruption of lineage-specific gene
expression programs. Thus, we hypothesize that imbalanced epigenetic antagonism between
the SWI/SNF and Polycomb complexes cause oncogenic transformation causing disruption of
lineage-specific gene expression programs. Our goal is to define the mechanism on how
mutations of SWI/SNF chromatin remodeling complex drive tumor formation and to identify
fundamentally novel therapeutic approaches for wide range of SWI/SNF mutant cancers.
In vivo cell fate tracker for stem cell therapy: from live to dead
Seung Koo Lee, Department of Radiology, Weill Cornell Medical College
Accurate tracing of cell viability is critical for optimizing delivery methods, and evaluating
efficacy and safety of cell therapeutics. A nanoparticle-based cell tracker was developed to image
cell fate from live to dead. The particle is fabricated from two types of optically quenched
polyelectrolytes, a life indicator and a death indicator, through electrostatic interactions. Upon
incubation with cells, the fabricated bifunctional nanoprobes are taken up efficiently, and the first
color is produced by normal intracellular proteolysis, reflecting the healthy status of the cells.
Depending on the number of coated layers, the signal can persist for several replication cycles.
However, as the cells begin dying, the second color appears quickly to reflect the new cell status,
and the vital status of cells, whether they are live or dead, can be identified clearly according to
their fluorescence color. Using this chameleon-like cell tracker, live cells can be distinguished
11
from apoptotic and necrotic cells instantly and definitively, and eventually feasible to image the
viability of implanted stem cells in vivo.
A draft map of the human proteome
Min-Sik Kim, McKusick-Nathans Institute of Genetic Medicine, Dept. of Biological Chemistry,
Johns Hopkins University School of Medicine
The availability of human genome sequence has transformed biomedical research over the past
decade. However, an equivalent map for the human proteome with direct measurements of
proteins and peptides does not exist yet. Here, we present a draft map of the human proteome
using high resolution Fourier transform mass spectrometry. In-depth proteomic profiling of 30
histologically normal human samples including 17 adult tissues, 7 fetal tissues and 6 purified
primary hematopoietic cells resulted in identification of proteins encoded by 17,294 genes
accounting for ~84% of the total annotated protein-coding genes in humans. A unique and
comprehensive strategy for proteogenomic analysis enabled us to discover a number of novel
protein-coding regions, which includes translated pseudogenes, non-coding RNAs and upstream
ORFs. This large human proteome catalog (available as an interactive web-based resource at
http://www.humanproteomemap.org) will complement available human genome and
transcriptome data to accelerate biomedical research in health and disease.
Arid3a is essential to execution of the first cell fate decision via direct embryonic and
extraembryonic transcriptional regulation
Catherine Rhee, Dept. of Molecular Biosciences, University of Texas at Austin
The first cell fate commitment in mammalian embryos to either the placenta-directed
trophectoderm (TE) or the embryo-destined inner cell mass (ICM) is controlled by antagonistic
actions of two transcription factors, Cdx2 and Oct4. Cdx2 represses pluripotency-associated genes,
such as Oct4 and Nanog in TE, whereas Oct4 represses TE-specific genes including Cdx2 in ICM.
Intensive studies in embryonic stem (ES) cells have identified numerous key regulators involved
in the establishment and/or maintenance of the ICM lineage. However, besides Cdx2, only a few
factors have been reported as regulators of the TE lineage, thereby limiting our understanding of
additional regulatory mechanisms required for execution of the first cell fate decision.
Arid3a, a transcription factor well-known for its requirement in B-lymphocyte development, has
recently been identified as a member of the ES cell pluripotency network. We found that Arid3a is
moderately expressed in ES cells, while its expression is significantly increased upon
differentiation. In particular, Arid3a is highly expressed in the extraembryonic tissues which
eventually give rise to the placenta, suggesting a putative role in placental development.
Consistent with these observations, Arid3a null mice undergo early embryonic death.
Here, we present evidence that Arid3a is a critical transcriptional regulator of ES to TS-like cell
trans-differentiation and plays an important role in the commitment and differentiation of TE,
rather than its specification. Induction of Arid3a in ES cells or in bona fide blastula-derived TS
12
cells triggers the TE specific gene expression program and differentiation towards subsequent
trophoblastic lineages, whereas KD of Arid3a compromises differentiation of ES cells. Arid3a OEgenerated TS-like cells when injected into 4-8 cell stage embryos, adopt an outside cell fate,
synonymous with commitment to the TE lineage. Intersection of global gene expression, genomewide target mapping and cellular localization studies revealed that, upon nuclear up-regulation,
Arid3a acts both directly upstream and parallel to Cdx2 to activate key TE-specific genes, while
directly repressing regulators of ES cell pluripotency, including Oct4 and Nanog. Arid3a and
histone deacetylases (HDAC1/2) associate at the protein level and selectively co-occupy
regulatory regions of pluripotent genes, suggesting a mechanism by which differential Arid3a
complexes contribute to execution of the first cell fate decision.
The role of p11: A cell type-specific regulation of depression
Ji-Seon Seo, Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University
Chronic stress responses may play additive and/or causative roles in the development of
physical or psychiatric diseases such as anxiety and depression. Chronic stress, especially, is
known to induce functional and structural changes in the medial prefrontal cortex, including the
prelimbic cortex (PrL). Chronic restraint stress suppresses glutamate receptor expression and
increases glutamate transporter expression in the PrL. Chronic stress-induced molecular, cellular,
and physiological alteration of the PrL may modulate depression phenotypes as a result of altered
connectivity and circuitry. Alteration in the PrL is seen both in rodent models of depression and
in depressed humans. Therefore, the PrL is likely to play an important pathophysiological role in
depression. However, little is known about cell type-specific molecular and cellular mechanisms
underlying these processes. Our previous studies have identified p11 (also known as S100A10)
and its binding molecules to be important regulators of depression-like states. However, the
expression and role of p11 in the PrL has not been studied. Our preliminary studies demonstrate
that both p11 mRNA and protein levels are reduced in the PrL following chronic restraint stressinduced depression, and these effects are rescued by antidepressant treatment. We also have
found that p11 is expressed in dopamine D2 receptor-positive neurons in layer II-III of the PrL
(D2-PrL neurons). To investigate p11's role in the PrL in relation to depression, we designed an
experimental scheme to determine 1) the functional role of p11 in D2-PrL neurons in depression,
and 2) the molecular mechanisms underlying the actions of p11 in D2-PrL neurons. Current and
future studies of p11 will provide not only an understanding of molecular and cellular
mechanisms on depression, but also a framework for the development of novel antidepressant
therapies.
Nek2-dependent activation of Kif24 in the suppression of primary cilia formation and breast
cancer development
Sehyun Kim, NYU Medical Center Cancer Institute, New York University
Most mammalian cell types have a primary cilium, which is a microtubule-based projection that
13
emanates from the surface of the majority of quiescent and differentiated cells. It serves as a
cellular 'antenna' for sensing and responding to the extracellular environment. Defects in the
cilium have been shown to cause a spectrum of diseases, ranging from developmental defects to
obesity to polycystic kidneys that are collectively recognized as ciliopathies. Defects in the
primary cilium may also promote tumorigenesis, since loss of cilia is commonly observed in
multiple types of cancer. Nonetheless, whether ciliary dysfunction is a cause or a consequence of
cellular transformation is unknown. Recently, several studies have reported Nek2 as an oncogene
that is ectopically expressed in various forms of breast cancer. Nek2 over-expression leads to
increased proliferation and drug resistance, whereas depletion of Nek2 reverts these effects,
although the role of Nek2 in breast cancer development is largely unknown. We have
preliminary data showing that suppression of Nek2 leads to increased formation of primary cilia,
which significantly retards cell proliferation. Conversely, over-expression of Nek2 leads to loss of
cilia in non-transformed cell lines, suggesting that Nek2 is a negative regulator of cilia formation.
We have also identified Kif24 as a putative substrate of Nek2. Kif24 has been identified in our lab
as a centriole-bound, microtubule depolymerizing kinesin that suppresses primary cilia formation.
tractBuilding on these observations, we hypothesize that Nek2 over-expression promotes
tumorigenesis by suppressing primary cilia formation through Kif24. We have evidence
showing that deregulation of Nek2-Kif24 in breast cancer cell lines restores primary cilia
formation, suggesting that the pathway may be associated with cellular transformation and
tumorigenesis. Furthermore, inducing cilia formation in these cells led to increased cellular
quiescence, which was rescued by elimination of cilia by co-depletion of pro-ciliary genes, Talpid3
and IFT88. This suggests that primary cilia formation may antagonize the uncontrolled
proliferative trait of breast tumors, and posits Nek2-Kif24 as a novel therapeutic target against
breast cancer.
14
2014 Fall Symposium Poster Presentation
Functional imaging reveals peripheral hypersensitivity during chronic pain, secondary
hyperalgesia
Yu Shin Kim, Dept of Neuroscience, Johns Hopkins University School of Medicine
Secondary hyperalgesia (one of chronic pain conditions), heightened pain sensitivity in uninjured
tissues surrounding an injury, is widely accepted to be mediated primarily by sensitization of
spinal cord and brain neurons, a process called central sensitization. The contribution of
peripheral sensitization of primary sensory neurons to chronic pain, secondary hyperalgesia
remains controversial. Here, we have generated Pirt-GCaMP3 mice in which GCaMP3, a geneticencoding Ca2+ sensitive indicator, is expressed robustly and specifically in almost all primary
sensory neurons. The advantages of GCaMP3 imaging using these mice include facile, parallel
direct visualization of activity in many afferents, excellent spatial resolution, and preservation of
somatotopic organization. Application of this technique to a trigeminal chronic pain, secondary
hyperalgesia model permitted us to visualize robust neuronal hypersensitivity in nerve fibers and
endings in the skin, cell bodies in trigeminal ganglion, and central terminals in the trigeminal
spinal nucleus. Strikingly, sensitization was observed not only in injured afferents but also in
uninjured trigeminal nerves of multiple neuronal cell and fiber types. Hypersensitivity in
uninjured large-diameter neurons innervating lamina III/IV at the central terminals was more
evident than that in the corresponding cell bodies. Pirt-GCaMP3 mice thus represent a unique
tool with which to visualize primary sensory neuron activity under physiological and
pathological conditions and to reveal peripheral sensitization mechanisms associated with
chronic pain, secondary hyperalgesia. Therefore, this study creates a new way of characterizing
the physiological properties and functions for developing new pain- or other modality-specific
drug target for a treatment with few side effects.
Suppression of the mevalonate pathway by wild type P53
Sung-Hwan Moon, Dept. of Biological Sciences, Columbia University
We previously reported that mutant p53 can transcriptionally activate the mevalonate (MVA)
pathway through an interaction with a family of transcription factors called sterol regulatory
element binding proteins (SREBPs) (Freed-Pastor et al., 2012). However, whether wild-type p53
regulates the MVA pathway remains to be elucidated. Our results show that wild-type p53
represses this pathway by an unexpected mechanism.
Activation of p53 by Nutlin-3 reduced expression of the MVA pathway genes in cells harboring
wild-type p53, but not in p53 null cells. When HCT116 p53+/+ and p53-/- isogenic cancer cells
were subject to sterol starvation, expression of MVA pathway genes was found to be significantly
higher in p53-/-, compared to p53+/+, and their induction was suppressed by addition of 25hydroxycholesterol or by Fatostatin, an inhibitor of SREBP activation. SREBPs are held as inactive
membrane-bound precursor proteins that are activated by proteolytic cleavage to form the
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mature polypeptides that are found in the nucleus associated with MVA genes. As assessed by
immunoblotting, loss of wild-type p53 was correlated with elevated levels of the mature form of
SREBP-2. In line with this, ChIP assay showed an elevated level of SREBP-2 occupancy at the
HMGCR promoter in p53-/-, compared to p53+/+. Importantly, maturation of SREBP-2 was
enhanced in HCT116 p21-/- and SK-HEP-1 transfected with p21 siRNAs, suggesting that p21 is
necessary for p53-mediated repression of the MVA pathway. Taken together, we propose that
wild-type p53 plays a suppressive role in the MVA pathway by maintaining mature SREBP-2 at
low levels through expression of p21.
Identifying the detrimental roles of IL-1 for host resistance against non-healing cutaneous
Leishmaniasis
Sang Hun Lee, Laboratory of Parasitic diseases, National Institutes of Health
Although infection with most L. major strains including Lm Friedlin (LmFn) can successfully be
resolved in C57BL/6 mice, West African Lm Seidman strain (LmSd) causes a non-healing lesion
and severe pathology in the inoculated ear dermis by immune responses that remain to be
elucidated. We recently demonstrated that inflammasome or IL-1 deficient mice displayed
complete resistance to LmSd infection. LmSd induces stronger activation of inflammasome and
production of IL-1 than LmFn. This ability of LmSd is due to more efficient phagocytosis of
LmSd than LmFn because there is no difference in IL-1 production with the comparable
phagocytosis of both parasites using full opsonization. Moreover, in vivo disease severity of
genetic hybrids of LmSd and LmFn is correlated with the efficiency of their phagocytosis. We
also found that both L. major strains can produce two waves of IL-1 which are initiated by two
different sensors of inflammasome. The initial burst of IL-1 is produced as early as 2 hours post
infection as the result of membrane damage and K+ efflux which is sensed by NLRP3. The
identity of second wave of IL-1 is still under active study. Thus we identify a detrimental role of
inflammasome activation in host resistance against L. major Sd and describe the molecular
mechanisms underlying its non-healing pathology.
Extended serum half-life of urate oxidase by site-specific Albumination
Sung In Lim, Department of Chemical Engineering, University of Virginia
Albumin fusion/conjugation (Albumination) has been an effective method to prolong in vivo halflife of therapeutic proteins. However, its broader application to proteins with complex folding
pathway or multi-subunits is restricted by incorrect folding, poor expression, heterogeneity, and
loss of native activity. Therefore, site-specific conjugation of albumin to a permissive site of a
target protein should expand the utility of albumin as a half-life extender. We show here genetic
incorporation of a non-natural amino acid (NNAA) followed by chemoselective albumin
conjugation to improve pharmacokinetics without significant loss of efficacy. Urate oxidase (Uox),
a therapeutic enzyme for treatment of hyperuricemia, is a homotetramer with multiple surface
lysines, limiting conventional approaches for Albumination. Incorporation of p-azido-L16
phenylalanine into two predetermined positions of Uox allowed site-specific linkage of
dibenzocyclooctyne-derivatized human serum albumin (HSA) through strain-promoted azidealkyne cycloaddition (SPAAC). The bioorthogonality of SPAAC resulted in the production of a
chemically well-defined conjugate, Uox-HSA, with a retained enzymatic activity. In the
pharmacokinetic study in mice, Uox-HSA displayed biphasic elimination kinetics with t1/2,β of
12.6 h, which contrasts to monophasic elimination kinetics of the wild-type Uox with t1/2,α of 1.4 h.
Site-specific Albumination enabled by NNAA incorporation and orthogonal chemistry
demonstrates its promise for the development of long-acting protein therapeutics with high
potency and safety.
Dynamics of DNA (hydroxyl)methylation between Intestinal Stem and Differentiated Cell
Rinho Kim, Department of Genetics, University of Pennsylvania
DNA methylation is an epigenetic modification involved in development and cancer. 5methylcytosine (5mC) can be oxidized to 5-hydroxymethylcytosine (5hmC) by the TET 1-3
enzymes in mammals. It is known that lacking Tet enzymes are involved in impaired leaning and
memory in brain and hematopoietic cancer, their role in intestinal epithelial renewal remains
unknown. Here, we found that 5hmC was enriched in the differentiated regions using
immunochemistry. Next, we performed immunoprecipitation for hydroxymethylated DNA
followed by high-throughput sequencing in Lgr5-expressing stem cells and differentiated cells. A
group of genes that acquire 5hmC in differentiated cells was mainly related with metabolic
processes and associated with increased expression. Loss of Tet1 in intestinal crypt cause more
cysts and inhibits intestinal enteroid differentiation. These data suggest that conversion of 5mC to
5hmC might be a novel mechanism contributing to intestinal health and a good target for colon
cancer drug development.
Analysis of Gut Commensal IgA Coating in Antiphospholipid Syndrome
Woojin Kim, Department of Immunobiology, Yale School of Medicine
Background: The mucosal barrier is known to be “leaky” in gut autoimmunity. Consistent with
this phenomenon, recent studies showed a markedly abnormal IgA coating of fecal bacteria in
patients with inflammatory bowel disease. The IgA coating in non-gut autoimmune diseases,
however, is unknown. The antiphospholipid syndrome (APS) is an autoimmune thrombophilia
that is manifested by vascular thrombosis and recurrent miscarriages. Various pathogens have
been associated with transient antiphospholipid antibody production. We hypothesized that
members of the gut microbiota could represent a chronic trigger in antiphospholipid-positive
patients and that they exhibit heightened adaptive immune responses to the microbiota. The
objective of this study was to examine levels of IgA-coated fecal bacteria in APS patients over
time and profiling the microbial community composition.
Methods: 32 subjects were included thus far in this study: 15 APS patients, 5 patients with nonautoimmune thrombotic states, and 12 healthy normal donors (total of 17 controls). Stool and
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blood was collected longitudinally at three monthly time points. Dietary and medication changes
were recorded at each visit. Plasma samples were analysed for β2-glycoprotein I antibodies by
ELISA. Fecal DNA was isolated using a bead beater (Biospec) and phenol-chloroform extraction,
then PCR-amplified using barcoded primers targeting the V4 region of the 16S rRNA gene.
Samples were sequenced using 2x250bp paired-end reads on an Illumina MiSeq instrument. In
parallel, fecal homogenates were stained with PE-conjugated anti-human IgA prior to
fluorescence-activated cell sorting.
Results: The average of IgA-coated fecal bacterial levels in APS patients was 17.7% compared to
11.2% in controls. The range of IgA coating was larger in APS subjects (2.3 to 49.2%) as opposed
to control subjects (2.9 to 21.4%) suggesting heterogeneity within the APS group. The differences
between APS and controls were however statistically significant (p=0.03). Incidentally, we also
noted among the control group one patient with IgA deficiency without any fecal IgA coating of
bacteria that was excluded from this analysis.
Conclusion: Our preliminary analysis demonstrated marked interindividual variation of IgA
coating among the gut microbiota of APS patients. Importantly, the average fraction of IgAcoated gut bacteria from APS patients was significantly higher than that of controls, supporting
that several APS patients mount a stronger adaptive immune response to the microbiota. We
hypothesize that this phenomenon is either due to an intrinsically heightened host response or a
“leaky gut barrier” with secondary IgA overproduction. To our knowledge, this study represents
the first examination of fecal IgA coating in patients with non-gut autoimmunity that warrants
16S ribosomal RNA profiling of IgA-coated gut commensals.
MnO-catalyzed synthesis of quinoxalines derivatives as bioactive compound
Aram Kim, Department. of Bioengineering, Temple University
Quinoxaline derivatives are nitrogen containing heterocyclic compounds that have been utilized
as dyes, organic semiconductors, electroluminescent materials, and pharmacologically active
materials. In the context of human health and controlling biological processes, quinoxalines
exhibit antitumor, antiviral, antibacterial, antimicrobial, and anti-inflammatory activities
according to published results.
Iodine, copper, palladium, bismuth powder, zeolites, and graphites, in particular, have been
utilized as catalyst systems that can be employed as synthetic tools during the production of
quinoxalines.
This presentation will highlight the usage of multipodal manganese oxide nanocrystals as catalyst
materials during the synthesis of quinoxaline derivatives involving α-hydroxy ketones and 1,2diamines. Manganese oxide nanocrystals - synthesized through the thermal decomposition of a
Mn-oleate complex - are single crystalline materials with uniform multipodal structures (the
average distance between two pods are 47 ± 2 nm).
The as-synthesized bioactive quinoxaline derivatives will be subject to a future study involving in
vitro biological activities.
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Site-Specific Labeling on Ghrelin Receptor via Genetically-Encoded Unnatural Amino Acid
Minyoung Park, Sakmar Laboratory,The Rockefeller University
The ghrelin receptor (GhR), a class A G protein-coupled receptor (GPCR) is a key player in
regulating energy homeostasis. The relationship between GhR and its endogenous ligand, ghrelin,
thus has been investigated as a drug target for treating obesity and related diseases. However,
until now there is no available marketed therapeutic targeting the ghrelinergic system primarily
due to the lack of molecular level of knowledge of the GhR signal pathways. We therefore
decided to develop a tool to analyze interactions among components comprising the GhR
signalosome (e.g., GhR, ligands, G proteins, etc.). In our present study, constitutively active GhR
with its various ligands serves as a model system. After genetically encoding the unnatural amino
acid, p-azido-L-phenylalanine (azF), site-specifically in GhR expressed in mammalian cell, we
characterized and identified functional azFGhR variants. Using bioorthogonal labeling approach
via strain-promoted alkyne-azide cycloaddition we fluorescently labeled selected functional azFGhR variant and further confirmed that these labeled receptors remained functionally active in
detergents by using fluorecence-based assays. Complementing emerging information from static
crystal structures of heavily modified GPCRs, our labeling strategy will provide a straightforward
way of uniformly labeling target GPCRs at specific sites suitable for single molecule fluorescence
studies to monitor dynamic conformational changes of GhR with minimal perturbation. With
facile applicability to other GPCRs and effector proteins, this type of labeling approach can be
used to spatially dissect signaling pathways of GhR, ultimately allowing us to design fine-tuned
drugs for treating “diabesity” syndromes
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AWARDEES
2014 AWARDEES (FALL)
KASBP-DAEWOONG ACHIEVEMENT
Kinam Park, Ph. D. Purdue University
KASBP-DAEWOONG FELLOWSHIP
Dr. Kimberly H. Kim, Harvard University
Dr. Seung Koo Lee, Weill Cornell Medical College
Dr. Min-Sik Kim, Johns Hopkins University
KASBP-GREENCROSS FELLOWSHIP
Catherine Rhee, University of Texas at Austin
Dr. Ji-Seon Seo, The Rockefeller University
Dr. Sehyun Kim, New York University
PAST AWARDEES
KASBP-DAEWOONG ACHIEVEMENT
2009
2010
2011
2012
2013
Choung Un Kim, Gilead Sciences, Inc. (Kainos Medicine Inc, Korea, Current)
Chung K. (David) Chu, University of Georgia
Sung-Hou Kim, University of California, Berkeley
Dennis Choi (MD, PhD) Stony Brook Medicine and Stony Brook University
Joseph Kim Inovio Pharmaceuticals
KASBP-DAEWOONG SCHOLARSHIP
2006
2007
2008
2009
James J. Pai, Schering-Plough (Handok Pharmaceuticals, Korea, Current)
Young-Whan Park, Merck (National Cancer Center, Korea, Current)
Young-Choon Moon, PTC Therapeutics
Hong-Yong Kim, Novartis
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PAST AWARDEES (cont’d)
KASBP-DAEWOONG FELLOWSHIP
2006 Jaeki Min, New York University; Hahn, Kim, Princeton University;
Hye-Jin Park, Rutgers University
2007 Jisook Moon, Harvard University; Sung-Yeon Park, Rutgers University;
Seok-Geun Lee, Columbia University
2008 Heung Kyu Lee, Yale University; Jung-Hwan Kim, Rutgers University;
Min Sik Kang, Columbia University
2009 Jin-Ah Park, Harvard University; Je-Min Choi, Yale University;
Deok-Ho Kim, Johns Hopkins University
2010 JungMin Ki, Rockefeller University; Hyung-Wook Kim, NIH;
Se Jin Ahn, Harvard University
2011 Muri Han, University of California, LA; Hwanjong Jang, Boston College
2012 Jeong Ho Chang, Columbia University; Jaewoo Choi, Oregon State University
2013 Jang Eun Lee (University of Pennsylvania), Eun Chan Park (Rutgers University)
KASBP-HANMI FELLOWSHIP
2011 Hyung Jin Ahn, Rockefeller University; Chang-Hoon Cho, Abramson Research Center
2012 Yuna Kim, University of North Carolina; Hyun Seop Tae, Yale University;
In Hye Lee, NIH
2013 Ju-Hee Lee, Memorial Sloan-Kettering Cancer Center;
Kyeong-Ryoon Lee, Rutgers University; Man Ryul Lee, Indiana University
2014 Young Chan Cha (Wistar Institute), Min-Kyu Cho (New York University)
Lark Kyun Kim (Yale University), Yu Shin Kim (Johns Hopkins University)
KASBP-YUHAN FELLOWSHIP
2011 Ki-Young Kim, Boston University; Joong Sup Shim, Johns Hopkins University
2012 Yeamin Huh, University of Michigan; Sookhee Bang, University of Pennsylvania;
Jungho Back, Columbia University
2013 Dong Jun Lee (University of Chicago), Ingyu . Kim (Yale University),
Ja Yil Lee (Columbia University)
2014 Seouk Joon Kwon (Rensselaer Polytech Institute), Jeongmin Song (Yale University)
Jae-Hyun Yang (Harvard Medical School), Wan Seok Yang (Columbia University)
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PAST AWARDEES (cont’d)
KASBP-GREEN CROSS FELLOWSHIP
2011 Hansang Cho, Harvard Medical School; Sung Ung Kang, Johns Hopkins University;
Mi-Yeon Kim, Columbia University; Jae Young So, Rutgers University;
Sung-Yong Hwang, NIEHS/NIH
2012 Wonjin Jo, Drexel University; Hyo Jung Kang, Yale University;
Junghyun Lee, Columbia University; Yong Jae Lee, Yale University; Je-Hyun Yoon, NIH
2013 Yunjong Lee (Johns Hopkins University), Jun-Dae Kim (Yale University), Bae-Hoon Kim
(Yale University)
Ja Young Kim-Muller (Columbia University)
KASBP FELLOWSHIP
2009 Sang-Ho Choi, National Institutes of Health (NIH)
2010 Sang Ryong Kim, Columbia University; Tae-Sook Yoon, Rutgers University; Eun Mi Hur,
Cal. Tech.
KASBP-KSEA FELLOWSHIP
2013 Sung In Lim, University of Virginia
2014 Keun-woo Jin, Temple University
KASBP-KUSCO FELLOWSHIP
2008 Hyeon Ho Kim, National Institutes of Health; Takbum Ohn, Harvard Medical School;
Wona Joo, Wistar Institute
KASBP-KRICT FELLOWSHIP
2009 Seung-Shick Shin, Rutgers University; Un Ju Jung, Columbia University; Kyuwon Baek,
University of Pennsylvania
KASBP-KHIDI FELLOWSHIP
2010 Jae Hyun Bae, Yale University; Hee Yeon Cho, Boston College
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2014-2015 KASBP DIRECTORS
Title
Name
Affiliation
President
Youngsun Kim
VaxInnate
President Designated
Jae Uk Jeong
GSK
1st Vice President
Yun H. Choe
Lucas & Mercanti
2nd Vice President
Chang-Sun Lee
PTC Therapeutics
Executive Director
Suktae Choi
Celgene
Science Director
Eunsung Junn
Rutgers University
Program Director
K. Stephen Suh
Hackensack Med Center
General Director
Dongweon Song
Novartis
Financial Director
Seongwoo Hwang
PTC Therapeutics
Web Director
Alexander Kim
Merck
1st Membership Director
Jun Hyuk Heo
Merck
2nd Membership Director
Chris D. Lee
Bristol-Myers Squibb
Public Relations Director
Sahee Kim
RevHealth, LLC
YG Director
Diana Dahea You
Rutgers University
Legal Director
Elizabeth Lee
Lucas & Mercanti
Auditor
Hak-Myung Lee
Shire
Boston Chapter President
Sean Kim
Novartis
Connecticut Chapter President
Seungwon Chung
Pfizer
Philadelphia Chapter President
Yonghwan Jin
GSK
Washington DC Chapter President
Luke K. Oh
Questcor Pharmaceuticals
Councilor
Je-Phil Ryoo
NAL Pharmaceuticals
Councilor
Young-Choon Moon
PTC Therapeutics
Councilor
Hak-Myung Lee
Shire
Councilor
Yong-Hae Han
Enzychem Lifesciences
Councilor
Jae-Hun Kim
IFF
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2014-2015 SPONSORS FOR KASBP
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