The problem of glioblastoma
Glioblastoma is the most common malignant primary brain tumor in adults. Despite aggressive surgical resection, chemotherapy, and radiation therapy, this disease remains challenging with no cure. We are interested in the molecular mechanisms that control key features of glioblastoma biology. The long-term goal of my laboratory is to leverage these insights for the rational design of novel strategies against this formidable disease.
Our laboratory is interested in developing new strategies to accurately profile patient tumors, including multisector and region-specific approaches, utilizing single cell techniques. We are also focused on establishing new experimental model systems using canonical tumor mutations.
Therapy resistance is predominantly defined by epigenetic changes in tumor cells. Glioblastoma stem-like cells represent a dynamic and treatment-resistant cell state influenced by cell-intrinsic and -extrinsic cues. Our laboratory is interested in finding ways to disrupt the epigenetic state that defines these tumor-initiating cells. We are pursuing a variety of approaches, including high-throughput screening, pharmacology, biochemistry, genetics, and material engineering, to accomplish this goal.
Cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD+), which has a well-known role in oxidation-reduction reactions and is an essential component of signaling pathways as a co-factor for NAD+-dependent enzymes. The rate-limiting enzyme in NAD+ synthesis, NAMPT, is highly expressed in glioblastoma tumors. How the regulation of this enzyme interfaces with NAD+-dependent signal transduction networks remains poorly understood in glioblastoma.
Laser therapy, also laser interstitial thermal therapy (LITT), is a minimally invasive tool used by neurosurgeons to kill tumor cells. We have established a mouse laser therapy system to examine the ability of LITT to locally disrupt the blood-brain barrier and augment drug delivery. We are also interested in how LITT changes the tumor immune microenvironment.
Alice Turski (2012-2014). Received 2013 Summer Undergraduate Research Fellowship to work in my laboratory.
John Finlay (Summer 2015).
Simon Gunter (2015-2016).
Ross Buchman (Summer 2019).
Alicia Yang (2020-2022)
Day Steed (Summer 2022)
Tatenda Mahlokozera (2020). PhD thesis, MD-PhD program.
Sam Sun (2013-2016). Received the Alpha Omega Alpha Award (2013) and American Brain Tumor Association Summer Fellowship (2014) to work in my lab.
Ishita Chen (Summer 2013).
Diane Aum (2014-2016). Received the David Silbert Summer Research Fellowship to work in my laboratory.
Ramin Lalezari (2014-2016).
David Dadey (2016-2017).
Ioana Flores (2017).
Mounica Pataru (2016-2019). Awarded a NREF Summer Research Fellowship.
Rukayat Taiwo (2017-2019). Awarded a HHMI Medical Fellowship
Amit Gujar, PhD (2012-2017). Currently a Staff Scientist in Roel Verhaak Lab, Jackson Laboratories, CT.
Peter Sylvester, MD (2013-2017). Resident in Neurological Surgery, Washington University.
Ananth Vellimana, MD (2014-2018). Resident in Neurological Surgery, Washington University.
Ashwin Kamath, MD (2014-2018). Resident in Neurological Surgery, Washington University.
Zohny Zohny, MD (2014-2017). Currently a Fellow in Neurological Surgery, Saint Louis University.
Thomas Beaumont, MD (2014-2016).
Rory Murphy, MD (2013-2016).
Santhi Pondugula, PhD (2014-2017).
Brendan Fong, MD (2017-2019)
Afshin Salehi, MD (2017-2020)
Dan Hafez, MD, PhD (2019-2021)
Devi Annamalai, PhD (2016-2020)
Bhuvic Patel, MD (2019-2022)
Other notable studies