Mentor Areas
Research in our laboratory is focused on T cell biology and applications of genetically-engineered T cells to the treatment of disease.
Active research projects in my laboratory include:
1) Developing chimeric antigen receptors (CARs) for adoptive immunotherapy of cancer with enhanced function and improved safety.
2) Developing and applying synthetic immunoreceptors to the treatment of immune-mediated disease.
3) Exploring the role of co-stimulatory signals in directing T cell metabolism and the way this metabolism affects T cell function within tumors.
4) CRISPR/Cas9-based gene editing approaches.
Description:
CAR T-cell therapy, which genetically engineers T cells to express tumor-specific chimeric antigen receptors (CARs), has evolved into a clinically effective strategy for cancer treatment. Interleukin-2 (IL-2) is a cytokine released by T cells that is commonly used to improve T cell survival, function, and antitumor activity following CAR transduction. However, therapeutic use of IL-2 is limited by the pleiotropic effects of IL-2, which has been shown to induce both immune stimulatory and suppressive T cell responses as well as dose-limiting toxicities in patients. Recently, researchers have developed a novel method to reduce toxicity while reaping the benefits of IL-2 adjunct therapy called orthogonal IL-2/IL-2Rβ cytokine-receptor system (Sockolosky et. al.). The incorporation of this system into other CAR-modified T cells previously established as strong anti-tumor agents has potential to greatly improve both the safety profile and overall efficacy of CAR T cell immunotherapy.
Students will test the orthogonal IL-2/IL-2Rβ system in combination with CAR constructs, previously shown by the Milone lab to be effective in the treatment of hematological malignancies. By testing orthoIL-2 and orthoIL-2Rβ as a means of inducing expansion of select B-cell-targeting CARs in mice, I hope to evaluate whether this method shows comparable or superior in vivo activity to the traditional IL-2 receptor signaling system.
Students will gain skills in cell culture, lentiviral transfection, enzyme-linked immunosorbent (ELISA) assays, confocal microscopy, and in vivo mouse work
Preferred Qualifications
Prior research experience involving cell culture and PCR is preferred but not mandatory.
Details:
Preferred Student Year
First-year, Second-Year, Junior, Senior
Academic Term
Fall, Spring, Summer
I prefer to have students start during the above term(s).Volunteer
Yes
Yes indicates that faculty are open to volunteers.Paid
No
Yes indicates that faculty are open to paying students they engage in their research, regardless of their work-study eligibility.Work Study
Yes
Yes indicates that faculty are open to hiring work-study-eligible students.