Research Interests

2020 global cancer statistics estimate that urinary bladder tumors account for over 200,000 deaths worldwide each year, and represent the tenth most common type of cancer. Dr. Mitra's research is primarily directed at investigating the molecular biology of urothelial cancers, and how this information can be used to improve patient management and identify potential therapeutic targets. He is also involved in several research efforts that focus on other urologic malignancies. Some of his projects include:

Identification of gene expression profiles that predict bladder cancer outcome: Using medium-to-high throughput technologies, the Mitra lab has adopted pathway-specific and whole-genome approaches to profile markers implicated in major bladder tumorigenic pathways, some of which are represented in the figure below. Such studies employ advanced bioinformatics including genetic programming algorithms and analysis of large-scale transcriptomic data. Such strategies have been successfully applied to identify molecular signatures that can predict nodal metastasis and clinical outcomes in noninvasive and invasive bladder cancers.

Intra- and intercellular circuitry contributing to bladder tumorigenesis. A complex network of molecular signaling is involved in malignant transformation and tumor progression. Mitogenic signals from growth receptors (gray) on the cell surface are conducted along signal transduction pathways (molecules in black) to affect cell-cycle regulation (molecules in purple) and apoptosis (molecules in blue). This leads to gene-expression changes that are controlled by key transcription factors (yellow). The tumor cell also interacts with factors controlling angiogenesis (green) and invasion (orange). Reproduced from Mitra AP, Cote RJ; Annu Rev Pathol (4):2009 [PubMed]. See high resolution version of the above image here.

Understanding the effects of smoking and NSAID use on bladder cancer progression: The Mitra lab is investigating detrimental molecular effects of smoking on the urothelium and how it contributes to bladder cancer progression. Clinical studies are also being conducted to investigate the potential of non-steroidal anti-inflammatory drugs (NSAIDs) in lowering the risk of progression in bladder cancer.

Examining alterations in the p53 pathway in invasive bladder cancer: The role of p53 pathway alterations in invasive bladder cancer has been extensively investigated. However, discrepancies in the p53 gene and protein status have been noted in bladder tumors, and this has a bearing on patient outcome. The Mitra lab is conducting studies that try to define the reasons behind these discrepancies, and how they may impact patient management.

Analyzing the effect of p53 alterations on chemotherapeutic response in bladder cancer: The Mitra lab is involved in analysis of data from the international, multicenter p53-targeted therapy trial, the first clinical trial in bladder cancer that targeted a molecular lesion. This trial examined effects of p53 alterations on response to chemotherapeutic regimens that include the DNA-damaging agent, cisplatin (in addition to methotrexate, vinblastine and adriamycin). While the initial results were not encouraging, they were highly dependent on the tumor's p53 protein status that can only partially predict outcome. The team is delving deeper into the tumors' biology in an effort to identify stronger predictors of chemotherapeutic response in these patients.

Identifying prognostic clinical parameters and constructing predictive models for genitourinary malignancies: In partnership with other collaborators, the research team is working to define clinical predictors of oncological endpoints in large patient cohorts.