Panel Discussion

My research background and interests are centered on elucidating the effect of chemical structure and hierarchical arrangement of biohybrid supramolecular assemblies (peptide-, lipid-, nucleic acid-, and carbohydrate-based) on their interactions with biological systems, as well as developing ways to hijack or modulate these dynamic interactions to achieve highly specified and targeted cargo delivery. The ultimate goal of both my previous and proposed research is to address fundamental, critical issues in biomedical research and significantly advance human health. I am currently an American Cancer Society Postdoctoral Fellow in the Mirkin Group at Northwestern University, where I have developed nanoscale immunotherapeutics for the treatment of triple-negative breast cancer. As part of my research, I have elucidated fundamental design parameters that dictate the interactions of spherical nucleic acids (SNAs) with biological systems. I have used these parameters to design SNAs that localize in specific cells and biological tissues, as well as to control and modulate the biological response to SNAs. Prior to my postdoctoral work, I earned my Ph.D. in Chemistry at the University of California, San Diego under the guidance of Prof. Nathan Gianneschi, where I pioneered entirely new ways of targeting therapeutic cargo to tumors, using both peptide-polymer amphiphiles and mimics of long chain fatty acids. Cumulatively, my graduate and postdoctoral research has revealed that subtle changes to the three-dimensional arrangement of nanomaterials profoundly impacts their function as cancer immunotherapeutics. My future research program will build upon the skills I honed during my graduate and postdoctoral training and focus on the development of novel carbohydrate-based materials for applications in drug delivery, cancer therapy, and regenerative medicine.

Ph.D. Research

My graduate research with Professor Nathan Gianneschi at the University of California, San Diego, focused on the development of drug delivery systems that exploit features of the tumor microenvironment (TME) for tissue targeting. During my Ph.D., I pioneered two distinct tissue targeting strategies that enhanced the delivery of chemotherapeutics to tumor tissue. These approaches utilized: (1) upregulated tumor-associated enzymes within the extracellular matrix, and (2) naturally evolved interactions between long chain fatty acids (LCFAs) and serum proteins. My early thesis work utilized matrix metalloproteinases to accumulate polymeric nanomaterials within the TME.^1-4 This work enabled the delivery of multiple classes of theranostic cargo to tumor tissue, including the safe and effective delivery of paclitaxel to tumor tissue at 16-fold higher doses than that of the parent drug. My later thesis work utilized the uptake of human serum albumin (HSA) by tumors, as well as the high affinity binding of fatty acids to HSA, for improved drug circulation half-lives and targeted delivery.^5-7 In this strategy, the terminal carboxylic acid moiety is retained on long-chain fatty acids (LCFAs), while drug conjugation occurs on the opposite chain end of the LCFA. This results in a prodrug that closely mimics the structure and function of native LCFAs and binds to HSA with high affinity. This motif is a generalizable new route for the facile modification of drugs for engaging HSA without the need for complex nanoscale formulations or covalent modification of the protein. During my Ph.D., I served as a subgroup leader and was instrumental in establishing multiple collaborations across UC San Diego. I held multiple fellowships and was an NIH T32 Cancers in Nanotechnology Trainee. I was recognized for my thesis research with an Outstanding Dissertation Award from the UC San Diego Department of Chemistry and Biochemistry in 2018.

Postdoctoral Research

My postdoctoral research with Professor Chad Mirkin Northwestern University focuses on the development of nanoscale cancer immunotherapeutics. Specifically, I have explored how nanoscale arrangement of vaccine components impacts their function and delivery to immune cells and tumors in vivo, and how the composition of the cargo contained within the SNA affects the observed immune response.⁸ Furthermore, I am using these parameters to dictate the delivery of SNAs to both dendritic cells and tumors in vivo, as well as to control and modulate the immune response to SNAs. Importantly, I have found that the chemical composition of vaccine components, coupled with their three-dimensional nanoscale arrangement, dictates their physical stability and release kinetics in biological media, which in turn dictates their overall therapeutic function. As a subgroup leader in the Mirkin group, I have helped guide the research of more than 20 graduate students and postdoctoral fellows from diverse disciplines. One of my central roles in the Mirkin group has been to lead the writing of NIH R01 (and equivalent) grant proposals to support the group’s research. In addition, I have successfully secured an American Cancer Society Postdoctoral Fellowship to support my work.

Future Research

My independent career will focus on researching the biological properties and applications of chemically well-defined synthetic glycopolymers. To achieve this, I will apply my expertise in the synthesis and evaluation of biopolymer-containing materials (oligopeptide- and oligonucleotide-conjugates) to this largely underexplored third class of biopolymer. Carbohydrates, comprising approximately 80% of Earth’s biomass, are the main structural components of cells and tissues and are critical to the development of complex multicellular organisms. Many biological interactions are dictated by carbohydrates, including cell-cell recognition, cellular signaling processes, formation of biological networks, and uptake of extracellular materials. Moreover, carbohydrates play significant roles in disease progression and in modulating immunity. However, these important molecules remain rather enigmatic and, aside from a few key research efforts, have been largely overlooked in chemistry and materials science. This is because structurally complex carbohydrates have traditionally eluded synthesis of molecularly well-defined synthetic analogues. Building on recent, significant advances in solid phase carbohydrate synthesis and harnessing the power of controlled living polymerization chemistries, this program aims to pioneer a new class of synthetic glycopolymers, called carbohydrate-polymer conjugates (CPCs). This research will enable the systematic study of how glycopolymer structure impacts its biological function and answer important questions at the interface of chemistry and biology. With this knowledge in hand, novel carbohydrate-based biomaterials can be designed for applications in biology and medicine.

Teaching Interests:

My teaching interests encompass topics in biomolecular engineering, with a focus on drug delivery. Moreover, teaching a large survey course, such as Thermodynamics, is highly appealing, because it is a tremendous opportunity to reach large numbers of young students and get them as excited about science as I am. As part of my professional development and career as a faculty member, I want to build an upper division course entitled, “Hybrid Materials using the Biomolecules of Life.” The course curriculum will encompass the design, synthesis, characterization, and applications of polymeric and nanoscale materials built using peptides, nucleic acids, carbohydrates, and lipids.

References Cited: (For a full publication list, please visit: www.c-callmann.com/publications)

1. Callmann, C.E., Barback, C.V., Thompson, M.P., Hall, D.J., Mattrey, R.F., and N.C. Gianneschi*. “Therapeutic Enzyme-Responsive Nanoparticles for Targeted Delivery and Accumulation in Tumors.” Advanced Materials; 2015, 27, 4611.
2. Daniel, K.B.^#, Callmann, C.E.^#, Cohen, S.M.,* and N.C. Gianneschi.* “Enzyme-Responsive Nanoparticles Release Cargo Upon Exposure to Matrix Metalloproteinase and Reactive Oxygen Species.” Chemical Communications; 2016, 52, 2126.
3. Proetto, M.P., Callmann, C.E., Cliff, J., Szymanski, C.J., Hu,D., Evans,J.E.; Orr,G., Howell, S.B., and N.C. Gianneschi*. “Tumor Retention of Enzyme-Responsive Pt(II) Drug-Loaded Nanoparticles Imaged by NanoSIMS and Fluorescence Microscopy.” ACS Central Science; 2018, 4, 1477.
4. Battistella, C.^#, Callmann, C.E.^#, Thompson, M.P., Yao, S., Hayashi, T., Carson, D.A., and N.C. Gianneschi*. “Delivery of Immunotherapeutic Nanoparticles to Tumors via Enzyme-Directed Assembly.” Advanced Healthcare Materials; 2019, 1901105.
5. Callmann, C.E., LeGuyader, C.L., Burton, S., Thompson, M.P., Hennis, R.H., Barback, C.V., Henrickson, N.M., Chan, W.C., Jeremko, M.J., Yang, J., Garcia, A., Burkart, M.D., Gilson, M., Momper, J.D., Bertin, P.A., and N.C. Gianneschi*. “Antitumor Activity of Octadecanedioic Acid-Paclitaxel Complexed with Human Serum Albumin.” Journal of the American Chemical Society; 2019, 141, 11765.
6. Callmann, C.E., Thompson, M.T., Gianneschi, N.C., LeGuyader, C.L., Bertin, P.A. “Modified Cytotoxins and Their Therapeutic Use.” US10023581B2. Filed September 21, 2016. Granted July 7, 2018.
7. Callmann, C.E., Thompson, M.T., Gianneschi, N.C., LeGuyader, C.L., Bertin, P.A. “Modified Cytotoxins and Their Therapeutic Use.” US10286079. Filed March 22, 2017. Granted May 14, 2019.
8. Callmann, C.E., Cole, L.E., Kusmierz, C., Huang, Z., Horiuchi, D., and C.A. Mirkin*. “Lysate-Loaded Immunostimulatory Spherical Nucleic Acids.” Proceedings of the National Academy of Sciences; 2020, 117, 30, 17543.

^#donates equal contribution