Professor

Oncology Department, School of Medicine
Associate Director, Shared Resources, Sidney Kimmel Comprehensive Cancer Center
Director of Admissions, Cellular and Molecular Medicine

RESEARCH OVERVIEW

Research in the Casero Laboratory is focused on the role of polyamine and polyamine metabolism in normal and pathological conditions, including cancer. The overall goal of the laboratory is to develop means to exploit polyamine metabolism and function as therapeutic targets.

Two enzymes cloned by my laboratory important in disease etiology and drug response are spermidine/spermine N1-acetyltransferase (SSAT) and spermine oxidase (SMOX). Each of these enzymes have been implicated not only in the response to specific drugs targeting polyamine metabolism, but also appear to be the molecular links between inflammation, DNA damage, epigenetic changes, and carcinogenesis. Thus, they also represent promising targets for chemopreventive intervention.

The laboratory is also exploring the ability of combining polyamine depletion with epigenetically-targeted drugs to enhance antitumor immune response. This strategy has led to a significant enhancement of the anti-tumor immune response in normally immunologically cold tumor models.

Finally, our laboratory is exploring therapeutic strategies to treat the rare, X-linked syndrome know as Snyder-Robinson Syndrome (SRS). SRS-affected individuals possess a mutation in the spermine synthase gene resulting severely aberrant intracellular polyamine ratios resulting in a range of debilitating pathologies including osteoporosis, hypotonia, seizures, cognitive impairment, and developmental delay. Our recent studies indicate that specific treatment of cells from affected individuals can result in a rebalancing of the polyamine profiles, and we are now using animal models of the disease to determine if the disease phenotype can be effected by treatment.

Cancer Biology | Cell Biology | Cellular Stress and Cell Signaling | Genetics, Genomics and Gene Regulation | Translational Research

Selected Publications

Holbert CE, Cullen MT, Casero RA Jr, Stewart TM. Polyamines in cancer: integrating organismal metabolism and antitumour immunity. Nature Reviews Cancer, 2022.

Holbert CE, Foley JR, Murray Stewart T, Casero RA Jr. Expanded Potential of the Polyamine Analogue SBP-101 (Diethyl Dihydroxyhomospermine) as a Modulator of Polyamine Metabolism and Cancer Therapeutic. International Journal of Molecular Sciences, 2022.

Stewart TM, Foley JR, Holbert CE, Klinke G, Poschet G, Steimbach RR, Miller AK, Casero RA Jr. Histone deacetylase-10 liberates spermidine to support polyamine homeostasis and tumor cell growth. Journal of Biological Chemistry, 2022.

Holbert CE, Foley JR, Yu A, Murray Stewart T, Phanstiel O 4th, Oupicky D, Casero RA Jr. Polyamine-Based Nanostructures Share Polyamine Transport Mechanisms with Native Polyamines and Their Analogues: Significance for Polyamine-Targeted Therapy. Medical Sciences, 2022.

Furbish AB, Alford AS, Burger P, Peterson YK, Murray-Stewart T, Casero RA Jr, Woster PM. Identification and Characterization of Novel Small-Molecule SMOX Inhibitors. Medical Sciences, 2022.

Learn More

NCBI Bibliography | Faculty Profile | ResearchGate | LinkedIn