Research

Department Research Overview

USC Translational Genomics was founded in January 2016 under the leadership of John Carpten, Ph.D., and David W. Craig, Ph.D., who both came to Keck School of Medicine from TGen in Arizona. USC Translational Genomics includes a truly interdisciplinary team of biologists, geneticists, and data scientists working hand in hand with engineers, chemists, and clinicians across USC departments, campuses, and hospitals. Together, they work in the lab and behind the computer to advance our understanding of a range of diseases and disorders — from neurological diseases and rare genetic syndromes to adult and pediatric cancers — and in the clinic to produce practical applications. They are also committed to understanding why certain diseases and disorders are more prevalent among different populations.

John D. Carpten, Ph.D.

Dr. Carpten’s cancer research program spans many tumor types including, but not limited to, prostate cancer, breast cancer, colon cancer, brain cancer, and multiple myeloma, in addition to several forms of pediatric cancer. He was a lead author on the first genome wide scan for hereditary prostate cancer genes (Science. 1996 Nov 22;274(5291):1371-4.), and the identification of HOXB13 as the first true hereditary prostate cancer gene (New England Journal of Medicine. 2012 Jan 12;366(2):141-9.). He also led a landmark study, which culminated in the discovery of the AKT1(E17K) activating mutation in human cancers, published in Nature. This study received an “Exceptional” rating by the Faculty of 1000, placing the paper in the top 1% of published work worldwide in the area of biology in 2007. He has also helped to pioneer the area of cancer disparities with his leadership in the African American Hereditary Prostate Cancer Study (AAHPC) Network and his work in understanding differences in tumor biology from cancers derived from individuals of different genetic ancestries.

Dr. Carpten has also been involved in the development and application of high throughput genomic methods and technologies throughout his career. Currently, he has a major focus in Precision Medicine, where Next Generation Sequencing is being applied to interrogate the genomes and transcriptomes of tumors in a clinical setting to identify targetable events for select therapeutics (Molecular Cancer Therapeutics. 2013 Jan;12(1):104-16.) (PLoS Genetics. 2014 Feb 13;10(2):e1004135.). Towards these efforts, he coordinated the development of a CLIA-certified laboratory to support clinical genomic testing. This laboratory was later commercialized as Ashion Analytics, LLC. It is his hope that this work will one day lead to improvements in knowledge based therapeutics toward improvements in outcomes for cancer patients. To learn more about ongoing activities in his group, please see his Laboratory Page.

David W. Craig, Ph.D.

Dr. Craig’s expertise is in genomics, bioinformatics, and data analysis of high-throughput genomics data. His laboratory consists of both a wet-lab and dry-lab. Within his group, lab personnel have the opportunity to either specialize or become dual trained in bioinformatics and molecular biology. His group pioneered cost-effective GWAS methods leading to genetic associations reported in Science, Nature Genetics, and New England Journal of Medicine. His publications include some of the most significant papers addressing the challenges of data sharing and data privacy (Homer et al, PLOS Genetics 2008). Since 2006, his team has been developing tools based on NGS beginning with publishing one of the first papers for targeted variant calling in humans (Craig et al Nature Methods, 2008). In the past 8 years, they have published and collaborated on over 60 NGS publications balanced between the wet and dry-labs. During this time, he has served in several international genomics projects, including as a PI on a U01 responsible for developing bioinformatic pipelines for the Phase I and Phase II portions of the 1000 Genomes Project.

With collaborators, his group was among the first to implement NGS in molecular profiling for cancer patient treatment recommendations in a feasibility study in metastatic triple negative breast cancer (Craig et al., Mol Cancer Ther. 2013). Building upon this and other efforts his team developed an end-to-end platform for personalized medicine, NGS data management, analysis, and clinical genomic interpretation following CAP/CLIA guidelines. Within this framework, they completed analytical validation for integrated RNA/DNA analysis of tumor/normal sets. Community resources from these efforts included include a collaborative release of COLO829 tumor/normal sequencing reference sets. He also was a founding scientific director for TGen’s Center for Rare Childhood Disorders – a research clinic enrolling over 1000 individuals into a study developing integrative RNA/DNA approaches for identifying the germline genetic basis of disease. To learn more about ongoing activities in his group, please see his Laboratory Page.

Bodour Salhia, Ph.D.

Dr. Salhia is a translational genomics scientist with extensive knowledge and expertise in mechanisms that underlie tumorigenesis and tumor biology. She merges cutting edge genomics/epigenomics analyses with cell biological and functional studies towards the investigation of clinically relevant problems in human cancer. During her graduate training, she focused on understanding the molecular and cellular determinants of glioma invasion. Her post-doctoral work focused on the genomics and epigenomics of breast cancer metastasis and multiple myeloma. She also characterized the function of AKT1(E17K) in breast cancer and performed immunophenotypic analysis of breast cancer in North Africa. She has led and continues to lead numerous DNA methylation studies using a plethora of both array and sequencing based technologies to measure whole genome and targeted CpG methylation changes in a variety of cancer types. Dr. Salhia utilizes these data to develop DNA methylation liquid biopsies. Her lab is in the process of validating a DNA methylation liquid biopsy for breast cancer recurrence which would indicate patients with evidence of micrometastatic residual disease that are therefore likely to experience a recurrence. Dr. Salhia’s lab also has research efforts in experimental therapeutics of brain metastasis by utilizing patient-derived xenografts and cell lines to identify novel treatment methods for this dismal disease.

Brooke Hjelm, Ph.D.

Dr. Hjelm’s research focuses on two separate yet complimentary areas: (1) the utilization of next generation genomic, transcriptomic, and proteomic technologies to profile recurrent and/or refractory pediatric, adolescent, and young adult (AYA) cancer patients for clinical decision making; (2) the use of functional genomics to identify and interrogate the developmental and therapeutic aspects of sarcomas that predominantly arise in the pediatric and AYA populations. Her overall research interests are a reflection of my diverse training history. She has interest in rhabdomyosarcomas (RMS), desmoplastic small round cell tumors (DSRCT), Ewing sarcomas (EWS), and clear cell sarcomas (CCS). The relatively low mutation burden in numerous different types of sarcomas suggests that there are transcriptional and/or epigenetic mechanisms that drive these diseases. This is inline with recent studies suggesting that epigenetic dysregulation and altered developmental programing drive many pediatric malignancies. Moreover, the mechanisms by which sarcoma-specific oncogenic fusion genes initiate and/or sustain disease remains elusive. Her laboratory is dedicated to developing new biological tools and approaches to enable a functional genomics inquiry into these mechanisms as to reveal insight into the underlying biology of these sarcomas. Additionally, her lab interrogates patient derived material to better define the molecular characteristics of different sarcoma subtypes to enable more precise treatment strategies for these difficult diseases.

Zarko Manojlovic, Ph.D.

Dr. Manojlovic in an Assistant Professor in the department of Translational Genomics and the Director of the newly formed Keck Genomics Platform (KGP) at the Keck School of Medicine of University of Southern California.In his role as an Assistant Professor, Dr. Manojlovic has a continued interest in urothelial carcinomas, with a focus on utilizing next generation sequencing and “omics” to elucidate population and tumor heterogeneity, as well as tumor microenvironments at the nexus of informatics and functional biologics with direct clinical implications. Dr. Manojlovic plans to expand profiling and comprehensive molecular analysis of the organ-confined elusive low-grade heterogeneous urothelial carcinomas that escape standard treatments and escalate into aggressive high-risk tumors with a high rate of mortality. Furthermore, building on his previous experiences with continuous collaborations, Dr. Manojlovic is interested in interrogating the ancestral effects on disease progression and outcomes in the urothelial tumors. His group provides opportunities in dual training in functional bioinformatics, with emphasis on clinical biologics approaches. Dr. Manojlovic has a major focus on applications of high throughput genomics critical to elucidate the oncogenic transcriptomes and genomes to identify clinically targetable events under the umbrella of precision medicine. To learn more about ongoing activities in his group, please see his Laboratory Page.

Enrique Velazquez, M.D., Ph.D., M.P.H

Dr. Velazquez’s research involves two main components. First it integrates clinical and genomic data that is pulled from multiple sources, e.g. Electronic Health Records (EHR), by using big data management systems and big data analytic techniques. Second, it uses gene expression to discover genomic level biomarkers related to cognitive function in individuals with neurological disease. As a teacher, he leads classes in statistics, data analytics, and bioinformatics, and as a bench scientist, he has studied neurological conditions, transplantation immunology, and basic cell biology and mechanisms. As an epidemiologist, he’s committed to delivering precision public health, using genetic data to assess risk and inform prevention strategies for individuals and communities. As a native of Mexico, he is part of USC’s Translational Genomic’s efforts to build and learn from diverse populations in order to serve diverse populations. To learn more about ongoing activities in his group, please see his Laboratory Page.