David D. Tran, MD, PhD, Research Profile

Tran-bio-2

David Tran, MD, PhD, joined the University of Florida faculty in the spring of 2015. Prior to his arrival, he was the director of the adult neuro-oncology section in the oncology division and an assistant professor in the Department of Medicine at Washington University in St. Louis, Missouri.

Dr. Tran received his PhD in immunology from Mayo Medical School in Rochester, Minn. and is board certified in internal medicine and medical oncology.

He is a member of the American Medical Association, the American Society of Clinical Oncology and the Society for Neuro-Oncology.

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appointments: (352) 273-9000

Current Basic and Translational Research Activities Research Narrative

My research program is focused understanding the mechanism of cancer metastasis and dormancy. The epithelial mesenchymal transition (EMT) is now suggested to play an important role in the initial invasion during cancer metastasis. However, direct in vivo evidence is currently lacking. Our lab is interested in understanding how cancer EMT contributes to cancer metastasis, and if so whether it also regulates cancer dormancy, a phenomenon in which micrometastatic disease is present in multiple organs but clinically undetectable.

To answer these questions, we employ both cell-based systems as well as a novel genetic mouse model of cancer EMT. The goal is to dissect the relative contributions of cancer EMT to the different stages of metastasis from the initial invasion to dormant micrometastases and the subsequent development of macrometastases. We use several mouse models of cancer including breast and liver cancer.

The second major focus of the lab is to understand what role mesenchymal factors play in primary malignant brain tumors. A substantial number of glioblastoma (GBM) tumors express increased levels of mesenchymal factors such as Snaill and Twisti. Mesenchymal GBM are relatively more resistant to chemoradiation compared to the neuronal and proneuronal GBM subclasses. GBM cell lines overexpressing mesenchymal factors have significantly augmented invasive and migratory capacity, are more enriched in neuronal cancer stem-like cells, and are more resistant to cytotoxic chemotherapy. However whether these observations hold true in vivo ¡s unclear. To address this question directly, we are usiMy research program is focused understanding the mechanism of cancer metastasis and dormancy. The epithelial mesenchymal transition (EMT) is now suggested to play an important role in the initial invasion during cancer metastasis. However, direct in vivo evidence is currently lacking. Our lab is interested in understanding how cancer EMT contributes to cancer metastasis, and if so whether it also regulates cancer dormancy, a phenomenon in whichng the novel mesenchymal model in mouse models of GBM to 1) determine whether mesenchymal factors functionally effect gliomagenesis, 2) delineate the functional contribution of mesenchymal factors to invasive properties of GBM cells, and 3) define the role of mesenchymal factors in GBM’s resistance to cytotoxic and antiangiogenic agents.

The third major focus of the lab is in translational and clinical research to develop novel therapeutics in Neuro-Oncology. Several projects are on going including
1) next gen genomic and RNA sequencing of brain tumors to identify genetic response signatures to therapeutics in brain tumors. The long-term goal is to develop genomics-based personalized therapies in neuro-oncology;
2) novel approaches to induce local disruption of the blood brain barrier to enhance chemotherapy delivery;
3) immunotherapy of brain cancer;
4) Reprogramming of glioma stem cells to increase treatment response; and
5) biomarkers for disease assessment and pseudoprogression.

Current Clinical Studies:

2011-present Brain Tumor Bank: Analysis of Histological, Genomic, Molecular, and Clinical Factors in CNS Cancer: The Neuro-Oncology Group.
Role: Principle Investigator
Sponsor: Washington University

2011-present DCVax-Brain: Phase II in newly diagnosed GBM, using
DC vaccine in combination with adjuvant Temozolomide
Role: Principle Investigator
Sponsor: Northwest Biotech

2012-present CDX1 10- ACT IV: Phase III in newly diagnosed GBM, with Rindopepimut/GM-CSF (anti-EGFR v3 vaccine) with adjuvant Temozolomide
Role: Principle Investigator
Sponsor: Celidex

2012-present Novocure EF-14: Phase III in newly diagnosed GBM, with
NovoTTF-IOOA device in combination with standard radiation and Temozolomide
Role: Principle Investigator
Sponsor: Novocure

2012-present BTTCll-Ol: Phase III in high-grade gliomas, with Lacosamide for seizure prophylaxis
Role: Principle Investigator
Sponsor: Brain Tumor Trials Collaborative

2012-present BTTC11-02: Phase I/Il in recurrent high-grade gliomas with bevacizumab and vorinostat
Role: Principle Investigator
Sponsor: Brain Tumor Trials Collaborative

2012-present CDX 110- ReACT: A Phase II Study of RindopepimutlGM-CSF in Patients with Relapsed EGFRvIII-Positive Glioblastoma
Role: Principle Investigator
Sponsor: Ceildex

2012-present RTOG 0834, Phase III comparing radiotherapy alone with radiotherapy combined with temozolomide and with temozolomide alone in non-lp, 1 9q code leted anaplastie astrocytoma or oligoastrocytoma
Role: Co-investigator
Sponsor: RTOG

2012-present RTOG 0925, Phase II, Observation of the natural history of postoperative cognitive function, quality of life, and seizure control in patients with supratentorial low-risk grade II gliomas
Role: Co-investigator
Sponsor: RTOG

2013-present BTTCO9-O1: Phase 11(1 in recurrent high-grade gliomas with everolimus and sorafmib
Role: Principle Investigator
Sponsor: Brain Tumor Trials Collaborative

2013-present Open-label, phase 2 study of bevacizumab in children and young adults with neurofibromatosis 2 and progressive vestibular schwannomas that are poor candidates for standard treatment with surgery or radiation
Role: Principle Investigator
Sponsor: NF2 Consortium – Department of Defense

2013-present CALGB-A0221 101: Phase III randomized double blinded, placebo controlled study of amodafinil to reduce cancer- related fatigue in patients with glioblastoma multiforme
Role: Principle Investigator
Sponsor: CALGB

2013-present Novocure EF-19, A prospective, non-randomized, concurrent control, open label, post approval study of NovoTTF-1 OOA in recurrent GBM patients
Role: Principle Investigator
Sponsor: Novocure, Inc

2013-present Role of lp/19q codeletions, IDH1 mutations and TP53 mutations in pseudoprogression in gliomas
Role: Principle Investigator
Sponsor: Washington University

2013-present A pilot, single institutional study of using MRI-guided laser heat ablation to induce disruption of the peritumoral blood brain barrier to Enhance delivery and efficacy of doxorubicin in the treatment of recurrent glioblastoma Multiforme
Role: Principle Investigator
Sponsor: Washington University

2013-present CALGB A071 101: A Phase II Randomized Trial
Comparing the Efficacy of Heat Shock Protein-Peptide Complex-96 (HSPPC-96) Vaccine Given with I3evacizumab Versus Bevacizumab Alone in the Treatment of Surgically Resectable Recurrent Glioblastoma Multiforme
Role: Principle Investigator
Sponsor: CALGB

2013-present A Phase I Pharmacodynamic Study Of Proteasome Inhibition By Disulfiram In Patients With Glioblastoma
Role: Co-investigator
Sponsor: Washington University

2013-present A Phase II Study of the NovoTTF-100A System, Enhanced by Genomic Analysis to Identify the Genetic Signature of Response in the Treatment of Recurrent Glioblastoma Multiforme
Role: Principle Investigator
Sponsor: Washington University

2014-present N0577: Phase III Intergroup Study of Temozolomide Alone versus Radiotherapy with Concomitant and Adjuvant Temozolomide versus Radiotherapy with Adjuvant PCV Chemotherapy in Patients with ip/i 9q Co-deleted
Anaplastic Glioma
Role: Principle Investigator
Sponsor: Washington University