Jatinder Lamba, Ph.D., a professor in the department of pharmacotherapy and translational research in the University of Florida College of Pharmacy, has received a $3.3 million five-year R01 grant from National Cancer Institute to study the biology of acute myeloid leukemia, or AML.
The study, titled “Integrated Systems Biology of Pediatric AML,” aims to define the impact of the proteomic and metabolomic landscape of leukemic cells on patient risk stratification and therapeutic outcome. Understanding these two levels of molecular data in more detail could reveal additional layers of AML prognosis and lead to more effective treatments.
“We are very excited to initiate these studies as the results will expand our understanding of the systems biology of AML from currently three levels of molecular data to five levels of molecular data,” said Lamba, a member of the Cancer Center’s Cancer Therapeutics & Host Response research program. “This research will provide insights in the identification of prognostic markers for diagnostic testing and development of more effective combination therapies for this brutal malignancy. This innovative and rigorous approach will yield discoveries with potential for incorporation into a new clinical trial.”
AML is a rare, devastating and understudied malignancy with around 61,000 cases in the United States. Although intensive chemotherapy has been used for nearly four decades, about 65% of pediatric patients, 40% of adults aged 21 to 65 and 10% of patients over 65 survive five years after diagnosis.
As the Frank A. Duckworth Eminent Scholar Chair, Lamba’s research focuses on identifying, characterizing and clinically validating markers in the body that can predict therapeutic outcomes in patients with cancer. Working with the other investigators from St. Jude Children’s Research Hospital and Children’s Oncology group, this team have made significant progress in characterizing the genetic, transcriptomic and epigenetic landscape of pediatric AML. These three levels of molecular data, along with microenvironmental and other factors, are known to impact the proteome and metabolome of AML in clinically relevant ways.
However, more research is needed to understand the scope of this impact. Few studies have focused on creating a comprehensive evaluation of the proteome and metabolome of pediatric AML. One of the major goals of the project is to create the first integrated systems-level understanding of the molecular biology of AML. This understanding could help develop more effective strategies and improve the prognosis of pediatric AML.
As pioneers in the integrated analysis of the pediatric AML genome, methylome and transcriptome, Lamba and her collaborator Stanley Pounds, Ph.D., a member of the St. Jude faculty and director of biostatistics courses in the St. Jude Graduate School of Biomedical Sciences, are uniquely positioned to characterize the proteome and metabolome of pediatric AML. Once characterized, they will integrate them with the large repository of previously collected data for a series of multicenter clinical trials, as well as therapeutic drug databases. Given that most of the drugs target proteins, the study has the potential to identify novel drug targets, as well as provide more efficacious drug combinations and allow for drug repurposing.
These studies will be the first comprehensive evaluation of the pediatric AML metabolome and proteome from patients treated on three clinical trials. This research will lead to an innovative method of combining five forms of omic data with multiple clinical endpoints into an integrated analysis of pediatric AML biology and the most complete understanding of pediatric AML to date.
Other collaborators on the grant are Christopher Vulpe, M.D., Ph.D., a professor in the department of physiological sciences in the UF College of Veterinary Medicine and a member of the Cancer Center’s Cancer Therapeutics & Host Response research program, and Tim Garrett, Ph.D., associate professor in the department of pathology, immunology and laboratory medicine in the UF College of Medicine and a member of the Cancer Center’s Mechanisms of Oncogenesis research program.
Jatinder Lamba, Ph.D., was featured in a recent UF Genetics Institute faculty spotlight.