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With a Little Help from Her CTRI Friends

Hannah Carter

Bioengineer Hannah Carter, PhD

CTRI Helps Launch Career of Bioengineer Hannah Carter

November 22, 2013 - With support from UC San Diego's Clinical and Translational Research Institute (CTRI), bioengineer Hannah Carter, PhD, received the highly prestigious NIH Early Independence Award and recently began her transition to a junior faculty position at UC San Diego. Presently she is acquiring a research team and computational resources to delve into her project: Network approaches to identify cancer drivers from high-dimensional tumor data.

Carter, who received a PhD in biomedical engineering from the School of Medicine at Johns Hopkins University in 2012, uses computer modeling and technology to study genetic mutations in cancer to identify molecular signatures that could lead to novel ways to use cancer therapies.

The NIH Director's Early Independence Awards provide an opportunity for exceptional junior scientists to accelerate their entry into an independent research career by forgoing the traditional post-doctoral training period. Carter is one of 15 receiving the 2013 NIH award, and the first recipient from UC San Diego. The award and start-up packages from CTRI, as well as from UC San Diego's School of Medicine and Moores Cancer Center, support her as an assistant professor in UC San Diego's Department of Medicine, Division of Genetics, and help her create her laboratory and build a team.

"Hannah is a gifted young researcher who has shown tremendous promise. I'm delighted CTRI could help launch her career at UC San Diego," said Gary S. Firestein, MD, Director of CTRI, Dean and Associate Vice Chancellor of Translational Medicine at UC San Diego School of Medicine.

Carter's project proposes a new way to identify "driver" mutations by modeling how molecular changes detected in tumors rewire biological networks and change the behavior of tumor cells. Drivers push cells toward cancer while "passenger" mutations are by-products that don't contribute to cancer development.

"Discriminating drivers from passengers is a pressing need in cancer research and will be critical for understanding the molecular origins of tumors, identifying novel targets for drug development, uncovering mechanisms of resistance to therapeutics, and ultimately selecting the most effective therapies for patients," Carter said.

But the task of teasing out the differences between driver and passenger mutations in tumor genome sequencing can be daunting.

"When you actually want to evaluate someone's tumor and understand what is causing the disease, you have to sift through which of these mutations are passengers and can be ignored and which ones are important (drivers), and it's actually quite difficult," Carter said. "The average adult solid tumor usually has 40 to 80 somatic mutations that cause changes to protein amino acid sequences. That's just looking at the protein coding regions of the genome."

Cells work by having all types of proteins interacting with each other to mediate larger processes. "They form complexes, so just looking at how mutation affects individual proteins is not good enough," said Carter. This compelling research problem drew her to UC San Diego and to the lab of Trey Ideker, who is the Chief of Genetics at UC San Diego and studies genomics using network models. "I wanted to see how we can bring networks to this problem and try to understand the interface between how mutations alter protein activities and what the consequences are for protein-protein interactions."

Her work entails acquiring, processing and analyzing molecular data such as DNA sequences, and then figuring out how to visualize and interpret the results. "A lot of what I do is mine genomic data and use it to build models of the underlying biology in order to study how it is causing disease. It's essential to build models that accurately represent the biological system I am studying, whether I use machine learning or some basic statistical analysis," the junior faculty member said.

Initially, Carter will conduct computational work to generate an actual hypothesis and data, and then test those hypotheses. "In all likelihood, we will identify mutations that look like they have specific effects on processes within the cell," she said. "We will want to test those hypotheses in cell culture and possibly with mouse models to see if that is indeed what is happening and if we can target it with potential therapies." The long-term goal of the project is to better enable scientists to look at someone's tumor genome and recommend therapies.

She is optimistic that findings from her project will suggest ways in which existing cancer therapies can be repurposed based on molecular signatures, and lauded CTRI for ongoing support. "The CTRI services related to clinical trial design and management, and subject recruitment, as well as the creation of biorepositories, will be essential for translating findings from my lab to improved clinical outcomes for cancer patients," Carter said.

About UC San Diego Altman Clinical and Translational Research Institute:

UC San Diego Altman Clinical and Translational Research Institute (ACTRI) is part of a national Clinical and Translational Science Award consortium, led by the National Institutes of Health National Center for Advancing Translational Science. Established in 2010, ACTRI provides infrastructure and support for basic, translational and clinical research throughout the San Diego region to bring discoveries from the laboratory to the bedside, and facilitates training and education of the next generation of researchers. ACTRI carries out its activities in collaboration with institutional and corporate partners and currently has more than 1,500 members.