(4ed) Using Structure-Function Relationships to Engineer Therapeutics By Design

By understanding the structure-function relationships that underlie therapeutic interactions with targets, the potential exists to develop a generalizable approach to therapeutic design. This knowledge can enable the translation and application of biological mechanisms and processes to create platforms that can address a wide array of diseases. For example, elucidating and harnessing these relationships within the context of the immune system could enhance immune activation and targeted responses against foreign pathogens and cancers. However, to ensure widespread success of a therapeutic platform, we must first develop the proper tools for the investigation of such mechanisms, and then synthesize materials that leverage these findings. My future research group will work at the forefront of this area to chemically design and engineer purposeful materials that can elucidate cellular-level mechanisms as a direct consequence of structure. By engineering tools to uncover these insights, we can iteratively synthesize and guide therapeutic design to achieve effective clinical translation. My future group will employ expertise in nanoscience, biomaterials, and chemistry, to manipulate natural and synthetic biomacromolecules for the purpose of creating therapeutic platforms that lead to potent responses and translate across diseases.

Research Experience:

Postdoctoral Research: Developing Potent Cancer Immunotherapy and Infectious Disease Vaccines using Spherical Nucleic Acids

Advisor: Dr. Chad Mirkin; Dept of Chemistry; Northwestern University

By understanding and capitalizing on structure-function relationships at the nanoscale, I have focused on the design of potent cancer (Teplensky, et al., Submitted) and infectious disease vaccines. Specifically, my work uses 3D nanostructures called spherical nucleic acids (SNAs) and harnesses their modularity to selectively tune various parameters of vaccine design, such as spatial and kinetic control (Skakuj, Teplensky, et al., Submitted) and presentation to cells of vaccine components (stimulant and target molecules). By utilizing various types of targets for different immune cell types and disease systems, my work develops translatable and translational structure-function relationships in the pursuit of the best therapy.

PhD Dissertation: Metal-Organic Frameworks as a Platform for Therapeutic Delivery

Advisor: Dr. David Fairen-Jimenez; Dept of Chemical Engineering & Biotechnology; University of Cambridge, UK

Metal-organic frameworks (MOFs) are porous self-assembling materials composed of inorganic nodes and organic linkers, and are currently used for catalysis, gas separation, and gas storage. They have recently been applied to drug delivery applications because of their large pore sizes and highly modifiable surface properties and functionalities. MOFs can lower the required amount of active pharmaceutical ingredient, and can provide a more efficacious therapy through their ability to shuttle insoluble or unstable molecules into cells. My dissertation focused on the utilization of MOFs as a delivery platform to: 1) extend small molecule chemotherapy drug release time and minimize the “burst release effect” (Teplensky, et al., J. Am. Chem. Soc. 2017, 139, 7522) and 2) protect fragile biomacromolecules from degradation for intracellular delivery (Teplensky, et al., Chem. 2019, 5, 2926). Ultimately, my PhD research demonstrated the versatility and new utilization of an existing class of materials towards emerging applications in gene regulation therapy and improved chemotherapeutic delivery to reduce systemic side effects, and provided me expertise in chemistry of porous materials, biological engineering, and drug delivery materials development.

Selected Publications:

Teplensky, M. H., Dittmar, J. W., Qin, L., Wang, S., Zhang, B., Mirkin, C. A. “Spherical Nucleic Acid Vaccine Structure Markedly Influences Adaptive Immune Responses of Clinically-Utilized Prostate Cancer Targets.” Submitted.

Skakuj, K., Teplensky, M. H., Wang, S., Dittmar, J., Mirkin, C. A. “Chemically Tuning the Antigen Release Kinetics from Spherical Nucleic Acids Maximizes Immune Stimulation.” Submitted.

Distler, M. E., Teplensky, M. H., Bujold, K. E., Kusmierz, C. D., Mirkin, C. A. “DNA Dendrons as Universal Agents for Intracellular Delivery.” Submitted.

Teplensky, M. H., Fantham, M., Poudel, C., Hockings, C., Lu, M., Guna, A., Aragones-Anglada, M., Moghadam, P. Z., Li, P., Farha, O. K., Bernaldo de Quirós Fernández, S., Richards, F., Jodrell, D. I., Kaminski Schierle, G., Kaminski, C. F., Fairen-Jimenez, D. “A Highly Porous Metal-Organic Framework System to Delivery Payloads for Gene Knockdown.” Chem, 2019, 5 (11), 2926–2941.

Teplensky, M. H., Fantham, M., Li, P., Wang, T. C., Mehta, J. P., Young, L. J., Moghadam, P. Z., Hupp, J. T., Farha, O. K., Kaminski, C. F., Fairen-Jimenez, D. "Temperature Treatment of Highly Porous Zirconium-Containing Metal–Organic Frameworks Extends Drug Delivery Release” J. Am. Chem. Soc., 2017, 139 (22), 7522–7532.

Teaching Interests:

I am trained as a chemical engineer and have always enjoyed the perspective that this classical training has been able to provide me when approaching biological problems. For these reasons, I am qualified to teach traditional core chemical engineering coursework such as thermodynamics, reaction kinetics, and heat and mass transport. However, I look forward to bringing my biological perspective to the teaching of these core courses, specifically by developing problem sets for these classes with questions that nod to biological problems and applications. As an example, the immune system is filled with the transport of proteins and molecules that provide cues to other cells. The rate of cellular production of these molecules and their transport throughout the body can easily be included in the discussion during reaction kinetics and heat and mass transport core classes. As my passion stems from the intersection of fields and chemical engineering as a field is incredibly interdisciplinary, I also look forward to designing courses that reflect my research interests and experience, namely: immune engineering and signal transport and biomaterials development and characterization.

Teaching Experience:

Throughout my academic career, I have engaged in opportunities that allow me to excite and motivate students to learn science. As a postdoc, I currently mentor several graduate and undergraduate researchers. I lead a subgroup of ~20 postdocs, graduates, and undergraduates who focus on biological research. I facilitate weekly research-focused meetings to provide experimental feedback and assistance. In addition to this overall mentorship oversight, I directly mentor four graduate students ranging in years of experience from having just begun the degree to transitioning to a more senior student. During my PhD I was a research supervisor to two master’s students, which involved designing a reasonable and thought-provoking project that they could accomplish during one academic year. I trained them on laboratory equipment, but also importantly helped them think about science so that they would be asking questions that could lead them to future experiments. I also have experience designing a course, as I planned a summer-long session for middle and high school students called “Intro to Medicine,” which covered topics across biology, biochemistry, and biomedical engineering. This experience taught me how to design coursework and assignments, as well as how to engage a classroom for multiple hours.

Selected Awards:

2021, Selected Speaker, University of Washington Distinguished Young Scholars Seminar

2020, Selected Participant, MIT Rising Stars in Chemical Engineering

2020, Crain’s Chicago Notable Woman in STEM

2019-2020, NIH Ruth L. Kirschstein National Research Service Award T32 Postdoctoral Fellowship

2018-2021, International Institute for Nanotechnology (IIN) Postdoctoral Fellowship

2014-2018, Gates-Cambridge Scholarship for Graduate Studies