Professor And Department Chair
Professor And Department Chair
Over the course of his career, Dr. John Carpten has become renowned for his key discoveries and contributions in the fields of in cancer genetics and genomics. Due to his rare combination of expertise in germline genetics in cancer and other heritable disease, in somatic cancer genomics, in cell biology, and in precision medicine in both pediatric and adult conditions, Dr. Carpten is uniquely positioned to lead this exciting new endeavor. He was a lead author on the first genome-wide scan for hereditary prostate cancer genes published in Science.
Dr. Carpten was also among the early pioneers in the area of health disparities research with the goal of understanding the role of biology in disparate incidence and mortality rates seen among underrepresented populations. Through his leadership, the African American Hereditary Prostate Cancer Study (AAHPC) Network was conceived. This study has become a model for genetic linkage studies in underrepresented populations and led to the first genome wide scan for prostate cancer susceptibility genes in African Americans.
Dr. Carpten has also begun to apply next generation sequencing technologies for deep genomic profiling of tumors in a clinical setting. Dr. Carpten has also been a leader in cancer genome science and is among a small group of cancer geneticists with vast experience in both germline genetics and somatic tumor biology. This has included the application of high throughput genomic technologies such as microarray measurements of genotypes and somatic alterations, and Next Generation Sequencing technologies for genome interrogation. He and clinical partners performed a precision medicine study using whole genome and transcriptome sequencing on 14 metastatic triple negative breast cancers to identify therapeutically actionable events that were used for treatment recommendations. The resulting paper was the most cited article in the journal Molecular Cancer Therapeutics in 2014. He is recognized as a thought leader in precision medicine, as shown by a number of papers describing the results of clinical cancer sequencing studies in cancer patients.
Professor and Vice-Chair
Professor and Vice-Chair
David Craig serves as Vice-Chair of USC's new Department of Translational Genomics within the USC Keck School of Medicine. 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. He has published and collaborated on over over 100 publications within the area of human molecular genomics including publications in American Journal of Human Genetics, Science, Nature Genetics, and New England Journal of Medicine. His group has participated as a lead in several international genomics projects, such as the 1000 Genomes Project.
A major area of focus for the past six years has been the area of precision medicine. With our collaborators, our 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 my group, we developed an end-to-end platform for personalized medicine, NGS data management, analysis, and clinical genomic interpretation following CAP/CLIA guidelines. Within this framework, we completed analytical validation following FDA guidelines 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. With Drs. Vinodh Narayanan and Matt Huentelman, he also led the establishment of a research clinic (The Center for Rare Childhood Disorder; C4RCD.org) enrolling over 1000 individuals into a study developing integrative RNA/DNA approaches for identifying the germline genetic basis of disease.
Dr. Craig's laboratory has openings for post-doctoral fellows and graduate students, and can be reached at davidwcr at symbol usc.edu.
Dr. Bodour Salhia's laboratory and research are focused on understanding of the mechanisms that underlie tumorigenesis. Dr. Salhia's graduate training focused on understanding the molecular and cellular determinants of glioma invasion. Her post-doctoral was focused on applying genomics and epigenomics analysis to improve our understanding breast cancer metastasis and multiple myeloma, and this work helped her spearhead epigenetics research as a new faculty member at the Translational Genomics Research Institute in Phoenix. During this time, she conducted numerous DNA methylation studies using a variety of both array and sequencing based technologies to measure whole genome and targeted CpG methylation changes.
Now at USC, Dr. Salhia's group has consistently focused on applying genomic and epigenomic technologies to translational questions of clinically unmet need. While it is now well established that cancer is a consequence of genetic alterations, it is becoming increasingly clear that disruption of epigenetic mechanisms is also a hallmark of the disease. Those epigenetic mechanisms help control the expression of genes - whether they are turned on or off - without affecting the DNA sequence itself. Thus, whether a cell becomes cancerous depends not only on its genome (whether or not key genes are mutated), but also its epigenome (whether or not these genes are expressed appropriately). These epigenomes, as they are known, have become the focus of a rapidly emerging and important new area of cancer research.Inappropriate epigenetic activity plays a significant role in cancer development but, unlike DNA mutations, which are permanent, epigenetic changes can be reversed. This means that it may be possible to find a way to regulate inappropriate epigenetic activity or to get a gene that is inappropriately expressed due to epigenetic changes to begin functioning normally again.
Addressing this area, her labs current focus is on identification and validation of DNA methylation biomarkers detected in cell-free DNA, which can be used to determine which breast cancer patients have the highest likelihood of recurring. Her group includes developing the necessary expertise in DNA methylation bioinformatics analysis and led the development of epigenetic analysis pipeline. Her group has extensive experience in preclinical testing and development of patient-derived xenografts (PDX) that can be used for testing novel therapeutic approaches in CNS metastasis.
Dr. McEachron'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. His overall research interests are a reflection of diverse training history. His training background in basic science includes the molecular dissection of autocrine and paracrine signaling mechanisms between tumor and host using in vitro and in vivo models and the characterization of genetically engineered mouse models of pediatric brain tumors. Additionally, his translational science training includes the interpretation and functional validation next generation sequencing data from recurrent/refractory pediatric cancer patients.
Dr. McEachron has gained an immense 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. His 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, we will interrogate patient derived material to better define the molecular characteristics of different sarcoma subtypes to enable more precise treatment strategies for these difficult diseases.