(2jk) Engineering Cytokines for the Treatment of Metabolic Diseases

RESEARCH INTERESTS

Cytokines are extremely powerful modulators of the immune system. However, cytokine therapies have had limited clinical success due to their poor pharmacokinetic profiles and pleiotropic nature. To circumvent current limitations and address this technology gap, my long-term research objective is to engineer cytokines to target specific cell populations without causing systemic immunomodulation. These targeted cytokine therapies have the potential to be administered systemically and act locally in a variety of contexts, thereby minimizing undesirable side effects.

Since macrophages play a central role in many inflammatory diseases and can be polarized toward anti-inflammatory or pro-inflammatory phenotypes, they represent a promising target for cytokine therapies. In response to certain pro-inflammatory stimuli, macrophages become metabolically dysfunctional, engulf excess low-density lipoprotein (LDL), and contribute to disease progression. Therefore, my future research group will target and reprogram these lipid-laden macrophages by engineering cytokines that hitchhike along with LDL. The Volpatti Lab will use this approach to develop novel cytokine-based treatments for atherosclerosis, cancer, and non-alcoholic fatty liver disease.

M.Phil. Research (University of Cambridge, Department of Chemistry, Advisor: Tuomas P. J. Knowles): My master’s thesis focused on the self-assembly of proteins into hierarchically structured materials. At the University of Cambridge, I developed expertise in microfluidic techniques (1), biophysical characterization (2), and protein fibrillation (3). Using droplet microfluidics, I fabricated protein microgels with localized tunable structures and properties and studied the formation of amyloid fibrils under different environments (4).

Ph.D. Research (MIT, Department of Chemical Engineering, Advisors: Dan Anderson, Bob Langer): The focus of my PhD research was the application of smart biomaterials as glucose-responsive insulin delivery systems. To this end, I synthesized stimuli-responsive polymers and formulated them into nanoparticles (5, 6) and microgels (7, 8) with glucose-sensing enzymes. I developed several biomaterial-based systems that rapidly respond to changes in blood sugar with changes in insulin release rate for enhanced glycemic control in diabetic animals.

Postdoctoral Research (University of Chicago, Pritzker School of Molecular Engineering, Advisor: Jeff Hubbell): During my postdoctoral studies, I have gained expertise in immunoengineering, protein engineering, molecular engineering, and immunometabolism. Using these skills, I rationally designed a polymersome-based COVID-19 vaccine (9), developed strategies to induce neoantigens in cancer cells (10), and engineered cytokines to target vascular inflammation in atherosclerosis (11).

Selected Publications:

(1) Volpatti LR and Yetisen AK. Commercialization of microfluidic devices. Trends Biotechnol. 2014, 7, 347-350.

(2) Volpatti LR and Knowles TPJ. Polymer Physics Inspired Approaches for the Study of the Mechanical Properties of Amyloid Fibrils. J. Polym. Sci. B Polym. Phys. 2014, 52, 281-292.

(3) Volpatti LR, Vendruscolo M, Dobson CM, Knowles TPJ. A Clear View of Polymorphism, Twist, and Chirality in Amyloid Fibril Formation. ACS Nano. 2013, 7, 10443-10448.

(4) Volpatti LR, Shimanovich U, Ruggeri FS, Bolisetty S, Müller T, Mason TO, Michaels TCT, Mezzenga R, Dietler G, Knowles TPJ. Micro- and nanoscale hierarchical structure of core-shell protein microgels. J. Mater. Chem. B. 2016, 4, 7989-7999.

(5) Volpatti LR, Matranga MA, Cortinas AB, Daniel KB, Langer R, Anderson DG. Glucose-Responsive Nanoparticles for Rapid and Extended Self-Regulated Insulin Delivery. ACS Nano. 2020, 14, 488-497. (ACS Editors’ Choice Article)

(6) Volpatti LR, Burns DM, Basu A, Langer R, Anderson DG. Engineered insulin-polycation complexes for glucose-responsive delivery with high insulin loading. J. Control. Release. 2021, 338, 71-79.

(7) Volpatti LR, Facklam AL, Cortinas AB, Lu Y-C, Matranga MA, MacIsaac C. Hill M, Langer R, Anderson DG. Microgel encapsulated nanoparticles for glucose-responsive insulin delivery. Biomaterials. 2021, 267, 120458.

(8) Volpatti LR, Bochenek MA, Facklam AL, Burns DM, MacIsaac C, Morgart A, Walters B, Langer R, Anderson DG. Partially oxidized alginate as a biodegradable carrier for glucose-responsive insulin delivery and islet cell replacement therapy. In Revision

(9) Volpatti LR*, Wallace RP*, Cao S*, Raczy MM*, Wang R*, ..., Hubbell JA. Polymersomes Decorated with the SARS-CoV-2 Spike Protein Receptor-Binding Domain Elicit Robust Humoral and Cellular Immunity. ACS Cent. Sci. 2021, 7, 1368-1380. *Equal contribution

(10) Volpatti L, Williford J-M, Montiel M, Hubbell J, Rosenthal J. Methods of inducing neoantigens in tumors. Patent Application.

(11) Volpatti LR, Reda J, Borjas G, Watkins E, Nguyen M, Solanki A, Zhou Z, Fang Y, Hubbell JA. LDL-Targeted IL-10 Suppresses Vascular Inflammation in Murine Models of Atherosclerosis. In Preparation.

Successful Proposals:

- American Heart Association Postdoctoral Fellowship (2021)

- University of Cambridge International Fellowship (2014)

- NSF Graduate Research Fellowship (2013)

- Whitaker International Fellowship (2013)

Selected Awards:

- Investigator in Training Award Finalist, American Heart Association (2022)

- T32 Postdoctoral Fellowship, NIH NHLBI (2020-2022)

- Poster Competition First Place Winner, Immune Modulation and Engineering Symposium (2020)

- Virtual Flash Talk First Place Winner, Controlled Release Society (2020)

- Best Presentation Award (Tie), Distinguished Young Scholars Seminar, University of Washington (2019)

- Bioinspired & Biomimetic Delivery Focus Group Trainee Award, Controlled Release Society (2019)

- Graduate Women of Excellence Award, MIT (2019)

- Priscilla King Gray Award for Public Service, MIT (2019)

- Change-Maker Award for combating sexual misconduct, MIT (2019)

Selected Current Service:

- Guest Editor, Frontiers in Chemical Engineering, Women in Chemical Engineering Special Issue

- Communications Chair, Women in Chemical Engineering, AIChE (past Annual Meeting Chair)

- Co-Chair, Biomaterials for Drug Delivery, AIChE

- Postdoc Representative, Immuno Delivery Focus Group, Controlled Release Society

- Member, Alumni Board, University of Pittsburgh Honors College

- Manuscript Peer Reviewer: ACS Central Science, ACS Omega, Advanced Drug Delivery Reviews, iScience, Journal of Controlled Release, Trends in Biotechnology

TEACHING INTERESTS

Throughout my academic career, I have sought out teaching opportunities with the goals of increasing my students’ intrinsic motivation and helping them develop critical thinking and problem solving skills. As an undergraduate, I taught a seminar course for freshman engineering students and developed a day-long workshop to introduce underrepresented minority middle school students to engineering. During my PhD, I was a teaching assistant for a polymer laboratory class for which I developed a novel laboratory module on glucose-responsive polymers and a freshman-level course to introduce students to chemical engineering concepts. To build upon my teaching experiences, I completed the Kauffman Teaching Certificate Program at MIT, which included 16 hours of formal instruction on course development and best teaching practices. I also served as a Teaching Development Fellow and Communication Lab Fellow for which I developed workshops on pedagogy and science communication, respectively. I am also interested in science communication and engineering education and thus helped build and evaluate the effectiveness of the MIT Chemical Engineering CommLab, a discipline-specific peer coaching program (Volpatti LR, et al. Quantitative Assessment of Students’ Revision Processes, 2020 ASEE Annual Conference Proceedings. DOI: 10.18260/1-2--35117). Additionally, I helped develop mandatory inclusivity trainings for the department through the Graduate Women in Chemical Engineering group that I cofounded (Volpatti LR, et al. Promoting an Inclusive Lab Culture through Custom In-Person Trainings within an Engineering Department, 2020 ASEE Annual Conference Proceedings. DOI: 10.18260/1-2--35102).

With these experiences in addition to my undergraduate and graduate training and research in chemical engineering, I am prepared and excited to teach any core course with particular interest in Transport Phenomena and Thermodynamics as these subjects are integral to my research. I am also passionate about teaching bioengineering-related subjects and aim to develop an elective immunoengineering course with a focus on the rational design of systems based on biological interactions and transport. As promoting DEI in the classroom is essential for effective teaching, I will use evidence-based practices to foster an inclusive and supportive teaching environment.

For more information, visit my personal website: lisarvolpatti.com