2012 Program Booklet - MCD Biology - University of Colorado Boulder

26 TH MCDB Graduate Student Symposium 

DEPARTMENT OF MOLECULAR, CELLULAR, & 

DEVELOPMENTAL BIOLOGY 

OCTOBER 12 & 13, 2012

Welcome 

The MCDB Graduate Student Symposium is a biennial event held since 

1979 that brings together leading researchers in both academic fields and 

cutting-‐edge biotechnology enterprises for two days of stimulating talks 

and interaction between members of our local scientific community. 

The symposium is entirely student-‐organized, and as such, all the 

planning and fundraising is conducted solely by graduate students. We 

are delighted to announce the 26th MCDB Graduate Student Symposium 

on Translational Science and Medicine. The symposium will be held on 

October 12-‐13, 2012 at the new Jennie Smoly Caruthers Biotechnology 

Building at CU-‐Boulder. It will begin with a keynote speaker and reception 

on Friday evening, followed by several sessions on Saturday. We are 

delighted that you will be participating during this enjoyable weekend of 

science and discussion. 

Sincerely, 

MCDB Graduate Student Symposium Committee 

Carolina Daez, Kent Riemondy and Tess Shideler

Past MCDB Graduate Student Symposia 

1979 Membranes 

1980 Cell Motility 

1981 The Accuracy of Biological Processes 

1983 Evolution: Shaping Molecules, Microbes, and Complex 

Organisms 

1984 Contemporary Research in Plant Biology 

1985 The Role of Complex Carbohydrates in Cellular Function 

1987 Sex Determination 

1989 Pathogen Strategies: Evasion and Suppression of the Immune 

System 

1990 Life at the Edge: From Prebiotic Chemistry to 

Extraterrestrial Biology 

1991 Zen and the Art of Cell Cycle Maintenance 

1992 Evolution from the inside 

1993 The Self-‐Wiring Machine: Development and Functional Organ 

Systems 

1994 The Human Genome 

1995 Self vs. Non-‐Self: Modes of Organismal Recognition 

1996 Pattern and Polarity: Establishing Difference in Development 

1997 Chromatin Structure and Gene Expression: Beyond the 

Double Helix 

1998 The Molecular Mechanisms of Cellular Motility 

1999 Programmed Cell Death: Making a Graceful Exit 

2000 Astrobiology: Life in the Universe 

2002 Genomics and Beyond: DNA tells all? 

2004 Cancer Biology 

2006 Stem Cell Biology 

2008 Infectious Disease and Host-‐Pathogen Interactions 

2010 Neuroscience

Agenda 

Friday, October 12, 2012 

Time Location Event 

4.00-‐5.00 pm Butcher Atrium Registration 

5.00-‐5.10 pm Butcher Auditorium Welcome 

5.10-‐6.10 pm Butcher Auditorium Keynote: Bill Freytag 

6.10-‐6.55 pm Butcher Auditorium Jennifer Leeds 

6.55-‐9.00 pm Butcher Atrium Dinner & Reception 

Saturday, October 13, 2012 

Time Location Event 

8.00-‐9.00 am Butcher Atrium Breakfast and late 

Registration 

9.00-‐9.30 am Butcher Auditorium Keynote: Larry Gold 

9.30-‐10.15 am Butcher Auditorium Michael Yaffe 

10.15-‐10.35 am Butcher Atrium Coffee Break 

10.35-‐11:20 am Butcher Auditorium William Marshall 

11.20-‐12.05 pm Butcher Auditorium Stephen A. Williams 

12:05-‐1.15 pm Butcher Atrium Lunch and Vendor 

Exhibition 

1.15-‐2.00 pm Butcher Auditorium JoAnne Flynn 

2.00-‐2.45 pm Butcher Auditorium John T. Schiller 

2.45-‐3.15 pm Butcher Atrium Coffee Break 

3.15-‐4.00 pm Butcher Auditorium Jeffrey Settleman 

4.00-‐4.45 pm Butcher Auditorium Peter Jackson 

4.45-‐5.30 pm Butcher Auditorium William Sullivan 

5.30-‐7.00 pm Butcher Atrium Reception

Keynote Speaker: 

William Freytag, PhD 

Former Chairman and CEO, Myogen, 

Boulder, CO 

Title: Fifteen Years and $1.3 Billion Later 

Friday, October 12 

5:10 – 6:10 pm 

JSCBB Butcher Auditorium 

Abstract: 

It is the mission of pharmaceutical research companies to take the path from understanding a 

disease to bringing a safe and effective new treatment to patients. Scientists work to piece 

together the basic causes of disease at the level of genes, proteins and cells. Out of this 

understanding emerge “targets”, which potential new drugs might be able to 

affect. Researchers work to: (i) validate these targets, (ii) discover molecules (potential drug) 

that interact with the chosen target, (iii) test these new compounds in the lab and clinic for 

safety and efficacy, and (iv) gain regulatory approval and get the drug into the hands of 

doctors and patients. This whole process typically takes 10-‐15 years and an expenditure of 

$1.3 billion.

Jennifer Leeds, PhD 

Executive Director-‐ Antibacterial Discovery 

Infectious Diseases Area 

Novartis Institute for BioMedical Research 

Title: Discovery and development of LFF571, a 

novel antibacterial for the treatment of C. 

difficile infection. 

Friday, October 12 

6.10-‐6.55 pm 


Abstract: 

Antibiotics are among the most important advances in the history of modern medicine. 

Antibiotics transform deadly bacterial infections into curable diseases, and enable surgical and 

medical innovation in nearly every therapeutic area. However, the increasing use of 

antibiotics has contributed to the rise in drug resistant and multi-‐drug resistant pathogens 

both in the community and in the hospital setting. At the same time, the number of new 

agents to treat bacterial infections is diminishing, partly due to the difficulty in identifying ideal 

targets and chemical starting points as well as increasing challenges in treating patients with 

complex medical needs. New agents should be potent against organisms exhibiting clinically-‐ 

relevant drug resistant phenotypes. The discovery of new chemical entities targeting 

unexploited mechanisms of growth inhibition is one strategy to address this hurdle. This was 

the origin of the drug discovery program that led us to discover LFF571. LFF571 is a new 

chemical entity that is currently being evaluated for safety and efficacy in patients with 

Clostridium difficile infection. The discovery and early development program for this novel 

compound will be presented.

Keynote Speaker: 

Larry Gold, PhD 

Chairman, Founder, and CEO of SomaLogic 

Founder of NeXstar and Synergen 

Title: Empowering Students: The Good and 

the Ugly 

Saturday, October 13 

9:00 – 9:30 am 


Abstract: 

In 1973 or thereabouts Charlie Yegian died of leukemia. Charlie was a young professor in 

MCDB, he was my friend, and I missed him immediately and still miss him. He was a great 

teacheer. Jane Westlye and I arranged a Symposium to honor Charlie. It was a great 

Symposium. One of the speakers said about Charlie that "when he did an experiment it stayed 

done." There is no higher accolade for a scientist. 

I then had an idea, which was simple. We could continue to have Symposia like the one we 

had to honor Charlie, and I could help the students raise money (my specialty, apparently) and 

they could do the work and share the learning that came with putting on a science 

symposium. We have had great student-‐driven symposia and some that were just OK -‐ that is 

as it should be. We always have had good people come to speak. The tension (The Good and 

the Ugly") is built into the activity, and it has to be there. Students are young, and they have 

ideas that are, say, in progress -‐ that has to be there. Students posture, unlike faculty, who 

never posture.

Michael B. Yaffe, PhD 

Professor, Department of Biology 

Massachusetts Institute of Technology (MIT) 

Title: Systems Biology Approaches to 

Optimizing Cancer Treatment 


9:20 – 10:15 am 


Abstract: 

Most current anti-‐cancer drugs function by one of two general mechanisms: (1) targeting specific signaling 

molecules, particularly protein kinases and growth factor receptors; and (2) inducing cytotoxicity through DNA 

damage or disruption of the mitotic spindle. Targeted agents/signaling inhibitors, when used as 

monotherapies for cancer treatment are non-‐curative. Although these drugs can induce dramatic tumor 

regression, and occasionally prolonged remissions, the cancers invariably recur. Alternatively, cytotoxic 

therapies that damage DNA have a long history of successful use as anti-‐neoplastic agents. However, patient 

responses to DNA damaging drugs vary greatly, and heterogeneity within any single tumor can lead to the 

emergence of a resistant sub-‐population of cells. The DNA damage from exposure of tumor cells to these 

cytotoxic agents is processed by a complex interacting network of signaling pathways involving protein 

kinases, phosphoserine/ threonine-‐binding domains (14-‐3-‐3 proteins, FHA domains, BRCT domains), and 

ubiquitin/SUMO modifying enzymes. The outputs of these DNA damage-‐activated pathways must be 

integrated with additional extracellular and intracellular cues such as cytokines and growth factor signals to 

control the resulting cellular response – cell cycle arrest, DNA repair, apoptosis or senescence. How this array 

of diverse signals is functionally integrated and processed, and how these signal integration events can be 

influenced by combinations of anti-‐cancer therapies to enhance tumor cell killing is unknown. 

To address this, we have been developing systems biology-‐based models of DNA damage signaling 

where gene expression signatures, kinase activities, protein phosphorylation, and phosphoprotein-‐binding 

events for multiple signaling pathways are quantitatively measured at densely sampled points in time, along 

with cellular responses such as cell cycle arrest, autophagy, and apoptosis. The resulting large dataset of 

signals and responses are then related to each other mathematically using partial least squares regression, 

principal components analysis, and time-‐interval stepwise regression. We have used this approach to examine 

the response of breast cancer and osteosarcoma cells to DNA damaging chemotherapy and gamma radiation 

in the presence or absence of small molecule inhibitors of growth factor signaling pathways. The resulting 

models, built from thousands of signaling measurements and hundreds of cellular response assays, reveals 

surprisingly paradoxical context-‐dependent roles for the MEK-‐Erk and p38/MK2 kinase signaling pathways in 

controlling cell cycle arrest, apoptosis and senescence after DNA damage. Using this approach, we recently 

identified a novel time-‐staggered combination therapy in which EGFR inhibitor pre-‐treatment is used to 

dramatically enhance DNA damage-‐induced cell death in a subset of triple-‐negative breast cancers by dynamic 

re-‐wiring of apoptosis pathways. The results from these systems-‐based studies illustrate the importance of 

measuring time-‐dependent changes in signaling pathways in evaluating and optimizing the effects of anti-‐ 

cancer drugs, and show the utility of a new concept – therapeutic network re-‐wiring – in designing novel 

combination therapies with greater anti-‐tumor efficacy.

William S. Marshall, PhD 

President and Chief Executive Officer 

miRagen Therapeutics, Inc. 

Title: microRNA targeting as a novel approach 

to the development of cardiovascular 

therapeutics 


10:35 – 11:20 am 


Abstract: 

Alterations in the expression of specific microRNAs have been observed in several 

cardiovascular disease models and human clinical samples, providing an exciting potential for 

therapeutic intervention. Genetic deletion studies that have been recapitulated by synthetic 

antimiR dosing studies demonstrated that the inhibition of certain microRNA’s is sufficient to 

produce beneficial outcomes in relevant disease models. Targeting such microRNAs with 

short, high-‐affinity oligonucleotides has demonstrated significant promise, as this strategy 

benefits from the altered biophysical properties of the antimiR compared to traditional 

antisense or RNAi gene targeting approaches. These characteristics contribute to enhanced 

pharmaceutical properties of the antimiR. An overview of our lead programs will highlight 

several key pharmacological observations that help build confidence in the lead molecules as 

they advance towards human clinical evaluation.

Steven A. Williams, PhD 

Chief Medical Officer 

SomaLogic 

Title: The Voices of Life; Discovery of Protein 

Patterns in Health and Disease Using 

SOMAmers 


11:20 – 12:05 pm 


Abstract: 

Despite the exciting promises being made about personalized medicine enabled by genetic 

testing, it is an impossible task. This is because the environment is not genetic, and yet has a 

big (or perhaps I should say "supersize") influence on health and disease, and because outside 

of a cancer our genetics don't significantly change from the time when we are babies to the 

day we die. The ideal health measurement would be of low cost and would respond to both 

environment and changes in health status. Proteins -‐ as the downstream product of genetics 

and environment -‐ have the right characteristics but the available technologies have not been 

up to the task of measuring thousands of them across a difference in abundance from the 

lowest to the highest of tens of billions to one. A new type of reagent will be described -‐ the 

SOMAmer -‐ which has enabled us to overcome these issues, and which has driven 

unprecedented discoveries. Examples will be shown from the early detection of cancer! 

to cardiovascular disease, and how individual tests can be bundled together to enable the 

"wellness chip", with the intention of lowering the cost of healthcare and improving health 

outcomes.

JoAnne Flynn, PhD 

Professor, Department of Microbiology and 

Molecular Genetics 

University of Pittsburgh School of Medicine 

Title: Tuberculosis: Seeing is Believing 


1:15 – 2:00 pm 


Abstract: 

Tuberculosis is caused by Mycobacterium tuberculosis. Humans infected with this bacillus can 

present with active TB (symptomatic) or clinically latent (asymptomatic) infection. The factors 

that determine the outcome of infection are not fully understood. Active TB can present in a 

variety of ways, from mild to fulminant disease. Recently, we have proposed that latent 

infection also represents a spectrum of infections, and those that are “higher” on the 

spectrum of latency are more likely to develop reactivation TB. Using a non-‐human primate 

model of tuberculosis, we have assessed the factors and events that influence outcome of 

infection, and have used sophisticated whole-‐body imaging to track the infection. Our findings 

indicate that the spectrum of M. tuberculosis infection that exists in the population can also 

exist in a single host. Using imaging, immunology, bacteriology and modeling, we have data to 

demonstrate the heterogeneity of infection within a single host at the level of the granuloma. 

Data on the variability in granulomas will be presented. This variability has implications for 

development of drugs to effectively and efficiently treat tuberculosis, as well as vaccines to 

prevent infection or disease.

John T. Schiller, PhD 

Head, Neoplastic Disease Section 

Deputy Laboratory Chief 

Laboratory of Cellular Oncology 

National Cancer Institute, Bethesda, MD. 

Title: Understanding and Learning from the 

Success of Human Papillomavirus Prophylactic 

Vaccines 


2:00 – 2:45 pm 


Abstract: 

The development of antimicrobial vaccines is undoubtedly one of the greatest triumphs of 

biomedical research. Given the extraordinary effectiveness of vaccines against a wide array of 

bacterial and viral pathogens, the failure to develop effective vaccines against the most 

common sexually transmitted infections, especially HIV, has been both surprising and 

frustrating. The only notable exception is the development of prophylactic vaccines against 

genital human papillomaviruses (HPVs), the primary etiologic agents in an estimated 5% of 

human cancers, most importantly cervical cancer. In recently concluded clinical trials, the 

vaccines were safe and very effective at preventing sexually transmitted infection and the 

neoplastic diseases induced by the HPV types targeted by the vaccines. They are now licensed 

in many countries worldwide for the prevention of cervical and other HPV-‐associated cancers 

and various other hyperproliferative diseases. It is therefore interesting to examine why the 

HPV vaccines have succeeded whereas those targeting other sexually transmitted infections 

(STIs) have failed. In this seminar, I will briefly review the association of HPVs with human 

cancer and other neoplastic diseases, describe the composition of the two commercial 

vaccines and summarize their efficacy in clinical trials and their emerging effectiveness in 

general vaccination programs. Specific aspects of HPV molecular biology and vaccine 

composition that likely contribute to their remarkable success will then be discussed. Finally, I 

will speculate on how the lessons learned from the HPV vaccines might influence the future of 

vaccine development for other STIs, particularly HIV and herpes simplex.

Jeffrey Settleman, PhD 

Senior Director, Discovery Oncology 

Genentech 

Title: The Many Flavors of Resistance to 

Anti-‐Cancer Drugs 


3:15 – 4:00 pm 


Abstract: 

The recent clinical success experienced with several “rationally-‐targeted” anti-‐cancer drugs, such as 

the kinase inhibitors imatinib, erlotinib, crizotinib, and vemurafenib, has defined a paradigm shift in 

cancer therapy. However, despite the sometimes impressive clinical activity associated with these 

agents, progression during therapy is inevitable due to the acquisition of drug resistance. For many 

drugs, specific genetic mechanisms of resistance have been elucidated, and pre-‐clinical findings 

implicate additional non-‐genetic mechanisms. Moreover, accumulating evidence implicates 

heterogeneity within cancer cell populations in the response to drug treatment, posing an additional 

challenge to the development of effective cancer therapeutics. 

While modeling the acute response to various anti-‐cancer agents in drug-‐sensitive tumor cell lines, we 

consistently observed a small subpopulation of reversibly “drug-‐tolerant” cells. This drug-‐tolerant 

phenotype, associated with a distinct chromatin state, is transiently acquired and relinquished at low 

frequency by individual cells within the population, implicating the dynamic regulation of phenotypic 

heterogeneity in drug tolerance. The drug-‐tolerant subpopulation can be selectively ablated by 

treatment with chromatin-‐modifying agents, potentially yielding a therapeutic opportunity. These 

findings suggest that cancer cell populations employ an epigenetically-‐regulated dynamic survival 

strategy in which individual cells transiently assume a reversibly drug-‐tolerant state to protect the 

population from eradication by potentially lethal exposures. 

Cancer cells typically express multiple receptor tyrosine kinases (RTKs) that mediate signals that 

converge on common critical downstream cell survival effectors -‐ most notably, phosphatidylinositol 

3-‐kinase and mitogen-‐activated protein kinase. Consequently, increased RTK ligand levels, via 

autocrine tumor cell production, paracrine contribution by tumor stroma, or systemic production, 

could confer resistance to inhibitors of an oncogenic kinase with a similar signaling output. Using a 

panel of kinase-‐“addicted” cancer cell lines, we found that most cells can be “rescued” from drug 

sensitivity by simply exposing them to one or more RTK ligands. Among the findings with clinical 

implications was the observation that hepatocyte growth factor confers resistance to the BRAF 

inhibitor vemurafenib in BRAF mutant melanoma cells. These observations highlight the extensive 

redundancy of RTK-‐transduced signalling in cancer cells and the potentially broad role of widely 

expressed RTK ligands in innate and acquired resistance to drugs targeting oncogenic kinases.

Peter Jackson, PhD 

Staff Scientist: Research Oncology 

Genentech 


4:00 – 4:45 pm 


Research Focus: 

My laboratory has worked on the biochemistry of the cell cycle, including DNA replication and 

mitosis. Much of our effort has gone toward understanding how proteolytic degradation by 

the ubiquitin proteasome system regulates the cell cycle. 

We have made key contributions to understanding how proteins that regulate the cell cycle, 

called cyclins, accumulate and are destroyed in vertebrate cells and in eggs. A central finding 

was our discovery of inhibitors of E3 ubiquitin ligases and their role in cell cycle control. We 

have identified several critical factors regulating cyclins and have linked their misregulation to 

cancer, proliferative disease and senescence. We continue to define important regulators in 

mitosis and in the ubiquitin pathway. 

Our recent work has also focused on signaling through the primary cilium. The primary cilium 

is an organelle with critical roles in signaling in tissues including the retina, nervous system, 

kidney and sensory organs. The importance of the cilia in signaling was only recently 

appreciated, but this structure organizes a still unknown number of receptor systems. These 

pathways are genetically linked to important degenerative diseases including renal cystic 

disease, obesity, diabetes, retinopathies and cancer signaling. We have used proteomic 

approaches to define regulatory networks linked to proteins that are defective in human 

diseases called ciliopathies. We are looking for critical receptor classes linked to these diseases 

and evaluating the therapeutic opportunities presented by these receptors

William Sullivan, PhD 

Professor, Department of Molecular, Cell & 

Developmental Biology 

University of California, Santa Cruz (UCSC) 

Title: Wolbachia, African River Blindness, and 

Big Sur 


4:45 – 5:30 pm 


Abstract: 

Wolbachia are obligate, intracellular, bacterial endosymbionts present in over 60% of all insect 

species. Manipulation of host reproduction and efficient maternal transmission have 

facilitated the global spread of Wolbachia in arthropods. Wolbachia are also present in filarial 

nematodes and are the leading cause of River Blindness and Elephantiasis. Our lab has 

focussed on the molecular and cellular interactions that mediate Wolbachia replication and 

transmission through insect and nematode germlines. Our studies demonstrate that efficient 

germline transmission of Wolbachia requires a developmentally coordinated association with 

plus and minus end motor proteins followed by a stable association in conserved germline 

determinants. In addition, Wolbachia manipulates host chromatin remodelers and the cell 

cycle to its advantage. Surveys of wild Drosophila populations reveals Wolbachia also stably 

populates host somatic lineages including the adult brain. Consequently we were able to 

generate stably Wolbachiainfected Drosophila cell lines. This facilitated high-‐throughput cell-‐ 

based screens for small molecule compounds that specifically target Wolbachia. We descrbe 

the identification of Albendazole sulfone, an FDA approved metabolite of Albendazole, that 

specifically disrupts Wolbachia replication in Brugia malayi, the nematode associated with 

Elephantiasis and 

River Blindness.

Acknowledgements 

The MCDB Graduate Student Symposium is a collaborative effort that would not 

be possible without the contributions of numerous individuals including 

undergraduate and graduate students, faculty and staff. Their dedication and 

enthusiasm has helped shape the engaging and collaborative environment found 

in the MCDB department. 

Special Thanks: 

Wendi Howard, Lee Gutmacher and Jaime Birren: Finance assistance 

Kathy Lozier: Travel arrangements and event logistics 

Karen Brown: Event logistics 

Laura Garret (SOFO): Budget coordination 

Erik Hedl and Alex Laszlo Bagi: Website design and registration databases 

Jessica Daez: Symposium logo design 

Vicky Romano and Lee Silbert: JSC Biotechnology venue coordination 

Ken Krauter: Graduate student mentor 

Elizabeth O'Connell (Front Range Catering Company): Catering and rentals 

In addition, special thanks to the numerous volunteers: 

Every two years, the graduate students in the MCDB department at the University 

of Colorado, Boulder organize a scientific symposium. We are delighted that an 

overwhelming number of undergraduate and graduate students have volunteered 

their time and talents to help with this year’s symposium. Students helped 

coordinate the entire event, including choosing this year’s topic, inviting speakers 

and helping with the logistical planning. The result is a day and a half of 

stimulating talks and interaction between members of our scientific community. 

2012 Graduate Student Symposium Organizing Committee: 

Carolina Daez (3rd year, Winey lab) 

Kent Riemondy (5th year, Yi Lab) 

Tess Shideler (6th year, Odorizzi lab) 

In memoriam: 

Dr. David M Prescott Distinguished Professor Emeritus MCDB 1926-‐2011 

Dr. Richard Ham Professor Emeritus MCDB 1932-‐2011

Symposium Location 

Jennie Smoly Caruthers Biotechnology Building 

Butcher Auditorium 

University of Colorado, Boulder 

3415 Colorado Ave., 

Boulder CO 80303 

Symposium Parking Map

2012 PRESENTING SPONSORS

2012 PRESENTING SPONSORS 

Arts and Science Student Government (ASSG) 

Center for the Integrative Study of Work in Living Systems, 

UCB 

Council of Colleges and Schools (CCS) 

Student Group Funding Board (SGFB) 

Vice Chancellor for Student Affairs (VCSA) 

MCDB Undergraduate Club 

NIH Institutional Training Grant 

"Creative Training in Molecular Biology" GM-07135 

The Department of Molecular, Cellular 

and Developmental Biology

Notes:

2012 Program Booklet - MCD Biology - University of Colorado Boulder

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