(2gm) Spatial and Temporal Control of Immunobiologics for Disease Treatment

The field of immunobiologics has revolutionized the way we approach the treatment of various diseases including cancer and infectious diseases. Immunobiologics such as vaccine antigens and cytokines have demonstrated remarkable efficacy in harnessing the immune system for disease treatment. However, their application is not without challenges, as the broad and systemic distribution of these immuno-biologics can lead to off-target effects, limited bioavailability, and potential toxicity. As a faculty member, I will engineer novel platforms that integrate material science, drug delivery, protein engineering and synthetic biology approaches to achieve spatial and temporal control over the exposure to immunobiologics to maximize their therapeutic efficacy while minimizing the side effects. Specifically, I will (1) develop thermoresponsive depot-forming biopolymers for sustained release of vaccine antigens and stimulatory cues, (2) incorporate synthetic biology-based gene circuits to control the kinetics of the expression of immunobiologics from RNA therapeutics by small molecule drugs, and (3) design lipid nanoparticle formulations enabling tissue-specific and cell-specific delivery of RNA therapeutics (Figure 1). Through a multidisciplinary approach, I envision the development of next-generation therapies that can precisely target and modulate immune responses against cancer and infectious diseases enabling specificity, selectivity, and tunability. Throughout my graduate and post-graduate research, I have received comprehensive training and developed expertise in a wide range of areas, including drug delivery, nanoparticle design, biopolymers, thermoresponsive materials, immunoengineering, synthetic biology, and protein engineering. This diverse skill set uniquely positions me to carry out research at the interface of engineering and medicine.

Successful Proposals:

• NIH Kirschstein-NRSA (F32) Award, 2022-present
• Ludwig Postdoctoral Fellowship in Cancer Research, 2021

Research Experience:

• Postdoctoral Project: “Engineering small molecule regulated RNAs encapsulated in lipid nanoparticles for modulating immune responses to vaccines and immunotherapeutics”. Under the supervision of Dr. Darrell Irvine, the Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
• Ph.D. Dissertation: “Albumin binding drug delivery systems”. Under the supervision of Dr. Ashutosh Chilkoti, Department of Biomedical Engineering, Duke University
• Integrated B.S.-M.S. Dissertation: “Carbohydrate-based nanoparticles for delivery of chemotherapeutics”. Under the supervision of Dr. Fatemeh Atyani, Department of Pharmaceutics, Tehran University of Medical Sciences

Education:

• Ph.D., Duke University, Biomedical Engineering, 2018
• Integrated B.S.-M.S., University of Tehran (Iran), Biotechnology/Bioprocess Engineering, 2010

Selected Peer-Reviewed Publications:

• Yousefpour, P., Ni, K. & Irvine, D.J. Targeted modulation of immune cells and tissues using engineered biomaterials. Nature Review Bioengineering. 1, 107–124 (2023)
• Irvine D, Weiss R, Li Y, Lonzaric J, Yousefpour P. Control of replication and transcription of self-replicating RNA in response to small molecules. U.S. Provisional Patent Application No. 17231588; 2021.
• Yousefpour P, Varanko A, Subrahmanyan R, Chilkoti A. Recombinant fusion of glucagon‐like peptide‐1 and an albumin binding domain provides glycemic control for a week in diabetic mice. Advanced Therapeutics. 2020; 2000073.
• Yousefpour P, Ahn L, Tewksbury J, Bellucci JJ, Saha S, Li X, Chilkoti A. Conjugate of doxorubicin to albumin binding peptide outperforms aldoxorubicin. Small. 2019; 15(12):1804452.
• Yousefpour P, McDaniel JR, Prasad V, Ahn L, Li X, Subrahmanyan R, Weitzhandler I, Suter S, Chilkoti A. Genetically encoding albumin binding into chemotherapeutic-loaded polypeptide nanoparticles enhances their antitumor efficacy. Nano Letters. 2018; 18(12): 7784–7793.

Teaching Interests:

Teaching and mentoring are incredibly fulfilling components of an academic role and hold tremendous personal value for me as they allow me to make a meaningful impact on the lives of students, inspire their intellectual curiosity, and facilitate their overall development as future scholars and professionals. Throughout my academic journey, I have consistently embraced opportunities for mentoring and teaching, exemplifying my deep-rooted passion for these invaluable pursuits.

Teaching Experience

At MIT, I worked as a teaching assistant for the course "Engineering the Immune System in Cancer and beyond." At Duke University, I served as a teaching assistant for the courses "Modeling Cellular and Molecular Systems" and "Structure and Properties of Solids." Additionally, I obtained the Kaufman Teaching Certificate at MIT and completed the credited courses "Fundamentals of College Teaching" and "College Teaching & Visual Communication" at Duke University. My dedication and passion for teaching were acknowledged through the Bass Instructional Fellowship awarded by the Duke University Graduate School.

Mentoring Experience

Throughout my academic journey, I have gained considerable expertise in teaching and mentoring students, specifically within a research context. During my PhD, I had the privilege of mentoring four undergraduate students, two of whom I provided guidance and supervision for their theses. During my postdoctoral research at MIT, I extended my mentorship to three Research Support Associates and one undergraduate student. Additionally, I had the rewarding experience of guiding an undergraduate student through the MIT Summer Research Program, which offers research opportunities to students from underrepresented and underserved backgrounds.

In my role as a mentor, I place great emphasis on scientific rigor and transparency. I encourage my mentees to approach their research with meticulous attention to detail, critical thinking, and a commitment to producing reliable and reproducible results. In addition, to foster a sense of ownership and independence, I assign individual projects to my mentees and actively engage them in all aspects of the research process, including experiment design, implementation, data analysis, and the presentation of their findings. My mentees actively contributed to the projects, earning authorship on publications, and showcased their work through presentations at internal meetings and conferences. Witnessing their growth and accomplishments has been immensely fulfilling, and I am eager to continue advising and instructing students in my future role as a faculty member.