The Greehey Children’s Cancer Research Institute at UT Health San Antonio is on an impressive and rising trajectory as 2018 begins. This includes the recruitment of seven new faculty members, further bolstering the Alamo City’s thriving biosciences sector.
Extramural funding for the Greehey Institute totaled $11.1 million in the state fiscal year ending Aug. 31, 2017. The new investigators accounted for $1.1 million, or 10 percent, of those research awards. The new scientists are in various stages of establishing laboratories, boosting the number of active labs at the Greehey Institute to 17.
The Greehey Institute, originally established with funding from the state’s tobacco settlement, is the largest freestanding pediatric cancer research facility in Texas. The institute was named for San Antonio businessman and philanthropist Bill Greehey and his family after the Greehey Family Foundation’s $25 million transformative gift to UT Health San Antonio in 2007.
Under the leadership of Peter Houghton, Ph.D., professor of molecular medicine, the Greehey Institute has a National Cancer Institute-funded program project grant in childhood sarcomas (rhabdomyosarcoma, Ewing sarcoma and osteosarcoma). The goal is to develop novel, more-effective therapies for treating patients; program project grants enable multipronged approaches in research. Sarcomas are tumors that grow in bones, muscles, tendons, cartilage and other anatomic features such as nerves.
Biochemical structure experts
Assistant Professors David S. Libich, Ph.D., and Yogesh K. Gupta, Ph.D., are employing state-of-the-art approaches to study the structure and dynamics of protein systems that are implicated in childhood cancers.
Dr. Libich is utilizing nuclear magnetic resonance (NMR) spectroscopy to gain understanding of basic mechanisms operating in both healthy and cancerous cells. Originally from Canada, he has studied in New Zealand, Singapore and Canada, and at the U.S. National Institutes of Health.
UT Health San Antonio has a sophisticated NMR spectroscopy facility that was a key drawing card in attracting a young researcher of Dr. Libich’s potential and proven ability, Dr. Houghton said.
Dr. Gupta joined the Greehey Institute from the Icahn School of Medicine at Mount Sinai in New York City. His lab is studying epigenetic modifications that regulate transformation of cancer cells. In addition to NMR spectroscopy, his lab utilizes X-ray crystallography and other approaches to study cancer development.
UT Health San Antonio has a well-established X-Ray Crystallography Core Laboratory that is supported by the Office of the Vice President for Research.
Siyuan Zheng, Ph.D., assistant professor, joined the Greehey Institute from The University of Texas MD Anderson Cancer Center. He has extensive experience in the development of computational tools and mining of high-throughput datasets. His primary research focus is using data analysis to gain understandings about the cancer genome, the complete set of genes present in cancer cells.
Dr. Zheng’s recruitment is supported by $2 million from the Cancer Prevention & Research Institute of Texas (CPRIT).
“Dr. Zheng has already made important observations regarding the genetics of pediatric and adult adrenal cortical cancer and potential treatments. His strengths in computational biology will help us significantly enhance our Big Data and genomic research capabilities to study cancer development as a complex system,” Dr. Houghton said.
Xiaojing Wang, Ph.D., assistant professor, joined the Greehey Institute from Baylor College of Medicine. She was co-investigator on a National Cancer Institute-funded project to analyze data generated by proteogenomics, which is an area of science at the interface of proteomics (study of proteins and their biological functions) and genomics (study of genes and their functions). Dr. Wang participated in a proteogenomic data analysis center to better understand cancer biology and improve cancer treatment.
Katsumi Kitagawa, Pharm.D., Ph.D., associate professor, joined the Greehey Institute from Ohio State University. His lab is investigating the role of aneuploidy in the development of pediatric cancers. Aneuploidy refers to gains or losses of chromosomes from the normal chromosome set in cells, and is a characteristic of some cancer cells.
The Kitagawa lab is studying the mechanism of chromosome instability in pediatric tumors.
New cancer model
Myron Ignatius, Ph.D., joined UT Health San Antonio from Harvard University in 2016 and is utilizing a zebra fish model to study rhabdomyosarcoma, a childhood cancer of cells that normally develop into skeletal muscles. The Ignatius lab is demonstrating that cancer initiation and progression can be visualized in zebra fish, which are translucent and see-through, making it possible to view cancer development under a microscope in real time.
A recent Ignatius lab publication shows how two signaling pathways work together to establish treatment-resistant secondary tumors that are biologically different from the original tumor.
Dr. Ignatius is also supported by a $2 million CPRIT recruitment award.
Subapriya Rajamanickam, Ph.D., was elevated to the Greehey Institute faculty after serving as a postdoctoral fellow since 2010 in the labs of institute faculty Manjeet Rao, Ph.D., and Alexander Bishop, Ph.D. In the Rao lab, Dr Rajamanickam studied a potential therapeutic agent to treat triple-negative breast cancer. In the Bishop lab, she studied augmenting cytotoxic treatments of ovarian and breast cancer.
Each UT Health San Antonio faculty member in an organized research unit such as the Greehey Institute is also appointed in an academic department. Following are the departments of the new Greehey Institute recruits, all within the Joe R. & Teresa Lozano Long School of Medicine:
– Dr. David Libich, Biochemistry & Structural Biology
– Dr. Yogesh Gupta, Biochemistry & Structural Biology
– Dr. Siyuan Zheng, Epidemiology & Biostatistics
– Dr. Katsumi Kitagawa, Molecular Medicine
– Dr. Myron Ignatius, Molecular Medicine
– Dr. Xiaojing Wang, Epidemiology & Biostatistics
– Dr. Subapriya Rajamanickam, Molecular Medicine
Excerpts of message by Peter Houghton, Ph.D., whose work is supported by the Greehey Distinguished Chair for the Children’s Cancer Research Institute Director:
Development of new therapies for children with cancer presents unique challenges. The incidence of cancer in children is relatively low. In the United States, about 12,400 new cases are diagnosed annually in patients under 20 years old. Each year in Texas, almost 1,200 children and adolescents younger than 20 years of age are diagnosed with cancer, representing 10 percent of all pediatric cancers diagnosed in the U.S. Approximately 200 children and adolescents die of cancer each year, making cancer the most common cause of disease-related deaths for Texans from birth to 19 years of age.
Nationally, the overall cure rate for all childhood cancers is approaching 70 percent, and in many patients who ultimately fail to be cured, their initial response to the current standard of care (surgery, radiation therapy and chemotherapy) is good, with overall five-year event-free survival approaching 80 percent. However, current treatments often result in signi
ficant health problems with long-term consequences, including cardiac dysfunction and cognitive impairment. Further, high doses of chemotherapy with conventional agents have not significantly improved outcomes for patients with advanced or metastatic disease. Consequently, a new approach to developing effective, less-toxic therapy is required and will be the focus of a Pediatric Drug Discovery Initiative (PDDI) at the Greehey Institute.
Our current understanding of childhood cancers indicates that many childhood cancers are “driven” by oncogenic fusion proteins. These aberrant proteins are the products of the joining of two or more genes that originally coded for separate proteins. Initial projects of the PDDI include validating fusion proteins found in pediatric cancers as targets for drug development. The PDDI will build on programs of excellence already established at UT Health San Antonio and our sister UT System academic institution, The University of Texas at San Antonio, to create new capabilities unique in Texas.
See full message on Greehey Institute website.