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Cassandra E Callmann

· Assistant ProfessorVerified

University of Texas at Austin · Biochemistry and Molecular Biology

Active 2014–2026

h-index20
Citations1.7k
Papers4024 last 5y
Funding
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About

Dr. Cassandra Callmann is an Assistant Professor and CPRIT Scholar in Cancer Research in the Department of Chemistry at the University of Texas at Austin. She completed her B.S. in Biochemistry at West Chester University in 2012, followed by her M.S. in 2014 and Ph.D. in 2018 in Chemistry at the University of California, San Diego. Her graduate work was supported by fellowships from the Inamori Foundation, the ARCS Foundation, and the Cancer Researchers in Nanotechnology program (NIH R25T). She was recognized for her thesis research with an Outstanding Dissertation Award from UC San Diego's Department of Chemistry and Biochemistry in 2018. After earning her Ph.D., she served as an American Cancer Society Postdoctoral Fellow at Northwestern University. In 2019, she was selected as a CAS Future Leader by the Chemical Abstracts Service of the American Chemical Society. Her research focuses on carbohydrates, which are the main structural components of cells and tissues and play critical roles in biological interactions, disease progression, and immunity. She aims to pioneer a new class of synthetic glycopolymers called carbohydrate-polymer conjugates (CPCs), enabling systematic study of their structure-function relationships and the design of novel carbohydrate-based biomaterials for applications in biology and medicine.

Research topics

  • Biochemistry
  • Chemistry
  • Biology
  • Polymer science
  • Organic chemistry
  • Cell biology
  • Computational biology
  • Cancer research
  • Molecular biology
  • Materials science
  • Polymer chemistry
  • Biophysics
  • Genetics

Selected publications

  • Multivalent Glycopolymer Design Unlocks Antimicrobial Activity of 2‐Deoxyglucose

    Angewandte Chemie International Edition · 2026-04-09

    articleOpen accessSenior authorCorresponding

    ABSTRACT With the increasing prevalence of multidrug‐resistant (MDR) pathogens, last‐line therapeutics such as cyclic peptides are insufficient, underscoring the need for new classes of antimicrobial compounds with distinct mechanisms of action. Here, we report a novel approach to glycan‐derived antimicrobials that transforms 2‐deoxyglucose (2DG), benign small molecules, into a potent antibiotic through its multivalent display as a glycopolymer. Toward this end, we synthesized a 2DG derivative amenable to ring opening metathesis polymerization (ROMP) and evaluated the impact of both spacing between 2DG and polymer backbone, as well as degree of polymerization. Shorter linkers and lower degrees of polymerization yielded the most potent antimicrobial polymer, hereafter referred to as poly2DG. Significantly, poly2DG exhibits broad‐spectrum bacterial inhibition, including against MDR methicillin‐resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa , and Acinetobacter baumannii , with MIC 50 values as low as 0.2 µg/mL. No such effect is observed for “free” 2DG nor the polymer scaffold alone, underscoring the importance of multivalent presentation for 2DG antibiotic activity. Altogether, this work shows the ability to convert an inert small molecule into an antimicrobial agent by simple polymeric scaffolding is a straightforward and effective chemical approach to develop materials that circumvent MDR.

  • Polysaccharide Meets Polyoxazoline: Regio- and Stereodefined β-1,2-Linked Pseudo-polysaccharides via Controlled Cationic Ring-Opening Polymerization

    Journal of the American Chemical Society · 2026-02-03

    articleSenior authorCorresponding

    Polysaccharides exhibit remarkable stereochemical and regiochemical complexity, yet their natural heterogeneity produces differences in composition and material behavior that are difficult to control or predict. Here, we report a synthetic approach that overcomes these challenges through the controlled, cationic ring-opening polymerization of glucosamine-derived 2-oxazoline monomers, affording a new class of well-defined pseudo-polysaccharides, wherein each saccharide subunit is 1,2-N-linked through a nitrogen containing a pendant acyl group. Under optimized conditions using a benzyl-protected monomer (OBn–GlcOx) and a methyl tosylate initiator, polymerization proceeds to full conversion within 3 h at 75 °C with linear molecular weight growth, first-order kinetics, and low dispersity (D̵ ≤ 1.2), consistent with a controlled polymerization mechanism. The resulting polymers exhibit complete β-1,2-regio- and stereoselectivity, narrow molecular-weight distributions, and retention of chain-end functionality that enables chain extension to form diblock copolymers with 2-methyl-2-oxazoline. Following quantitative deprotection, the resulting polymer is water-soluble and both protected and nonprotected versions display markedly enhanced resistance to ultrasonic, acidic, and thermal degradation as compared to chitosan (mass loss ≤63% vs 93% under harshest conditions). These findings establish a synthetic route to stereoregular, amide-linked pseudo-polysaccharides with tunable physicochemical properties, expanding the accessible design space for well-defined, carbohydrate-based materials.

  • Multivalent Glycopolymer Design Unlocks Antimicrobial Activity of 2‐Deoxyglucose

    Angewandte Chemie · 2026-04-09

    articleOpen accessSenior author

    ABSTRACT With the increasing prevalence of multidrug‐resistant (MDR) pathogens, last‐line therapeutics such as cyclic peptides are insufficient, underscoring the need for new classes of antimicrobial compounds with distinct mechanisms of action. Here, we report a novel approach to glycan‐derived antimicrobials that transforms 2‐deoxyglucose (2DG), benign small molecules, into a potent antibiotic through its multivalent display as a glycopolymer. Toward this end, we synthesized a 2DG derivative amenable to ring opening metathesis polymerization (ROMP) and evaluated the impact of both spacing between 2DG and polymer backbone, as well as degree of polymerization. Shorter linkers and lower degrees of polymerization yielded the most potent antimicrobial polymer, hereafter referred to as poly2DG. Significantly, poly2DG exhibits broad‐spectrum bacterial inhibition, including against MDR methicillin‐resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa , and Acinetobacter baumannii , with MIC 50 values as low as 0.2 µg/mL. No such effect is observed for “free” 2DG nor the polymer scaffold alone, underscoring the importance of multivalent presentation for 2DG antibiotic activity. Altogether, this work shows the ability to convert an inert small molecule into an antimicrobial agent by simple polymeric scaffolding is a straightforward and effective chemical approach to develop materials that circumvent MDR.

  • Pd- and Cu-Cocatalyzed Anaerobic Olefin Aminoboration

    The Journal of Organic Chemistry · 2025-12-11

    articleOpen access

    , a combustion accelerator, as the terminal oxidant. Herein, we report an efficient Pd- and Cu-cocatalyzed aminoboration of unactivated olefins, employing benzoquinone as the terminal oxidant. These conditions allow for enhanced turnover frequencies and an improved substrate scope relative to those of other Pd-catalyzed aminoboration reactions. These highly practical, selective, and high-yielding aminoboration conditions overcome many of the challenges associated with ligand-free oxidative Pd catalysis. The representative scope of the reaction includes 50 examples. α-Olefins, internal vinyl arenes, and strained cyclic olefins all participate along with a wide variety of amine nucleophiles. Mechanistic investigations support the idea that the rapid rate of oxidation by benzoquinone and Cu(II) prevents the aggregation of heterogeneous Pd(0) species, allowing the Pd to remain homogeneous throughout the aminoboration reaction. The scalability of the reaction and the synthetic utility of the products are demonstrated.

  • Exploiting Metabolic Vulnerabilities in Cancer with a Dual-Transporter-Targeted 2-Deoxyglucose Analogue for Low-Dose, Potent Antitumor Activity

    Journal of the American Chemical Society · 2025-11-17

    articleSenior authorCorresponding

    Clinical translation of 2-deoxyglucose (2DG) as a cancer therapeutic has been precluded by the need for high systemic concentrations to outcompete circulating glucose, resulting in dose-limiting toxicity. Here, we overcome this barrier by covalently linking 2DG to 1,18-octadecanedioic acid (ODDA) to engage both glucose and long chain fatty acid transport pathways simultaneously. The resulting conjugate (2DG-ODDA) associates with serum albumin and leverages dual-transporter uptake by 4T1 triple-negative breast cancer (TNBC) cells. In vitro, 2DG-ODDA is highly potent as compared to the parent 2DG, with a 16-fold lower IC50 value. Analysis of how 2DG-ODDA exerts its cytotoxic effects revealed that the compound induces apoptosis consistent with glycolytic inhibition, as confirmed by metabolic flux analysis showing a significant decrease in glycolysis-derived ATP production. 2DG-ODDA treatment also significantly reduces the rate of mitochondrial ATP production by cells, indicating that the conjugate disrupts multiple cellular processes in its mechanism of action. Further analysis revealed that 2DG-ODDA is cleaved by α-mannosidases. In vivo, low-dose subcutaneous 2DG-ODDA treatment significantly suppresses tumor growth, whereas equimolar 2DG is inactive. Together, these findings establish dual nutrient-pathway targeting as a strategy to confer anticancer activity to otherwise ineffective glycolytic inhibitors by exploiting metabolic vulnerabilities in cancer.

  • Acid Hydrolyzed Nylon-6 Turbidity as a Novel, Efficient, and Adaptable Assay for Nylonase Activity

    ACS Synthetic Biology · 2025-12-08

    article

    The development of enzymes for plastic recycling is reliant on the ability to identify and engineer novel biocatalysts. Nylon-6 is a plastic for which there is great importance for recycling and valorization due to its use in textiles, automotive components, and engineered materials. High-throughput screening is increasingly the preferred method for enzyme engineering, and while high-throughput assays exist for nylonase activity, they suffer from a variety of pitfalls including dependence on complex instrumentation, utilization of nonrepresentative model substrates, inconsistent product derivatization, and sensitivity to pH and protein concentrations. Limitations in high-throughput nylonase screening correspondingly limit the number of variants that can be tested and thus hamper efforts to improve the relatively small number of nylonases known. Here, we demonstrate the utilization of acid oligomerized nylon-6 (AON6) to assay the performance of nylon-6 hydrolyzing enzymes in a manner that is compatible with purified protein and cell lysate while also allowing for variation in pH, solid loading, and enzyme concentration.

  • Comprehensive synthesis and anticoagulant evaluation of a diverse fucoidan library

    Nature Communications · 2025-05-10 · 17 citations

    articleOpen access

    Fucoidan, a sulfated glycan derived from brown algae, has garnered significant attention for its anticoagulant properties. However, the structural complexity and heterogeneity of naturally extracted fucoidan have hindered a comprehensive understanding of its structure-activity relationship, limiting the development of fucoidan-based anticoagulant drugs. To address this challenge, we synthesize a diverse library of 58 distinct fucoidans with multiple contiguous 1,2-cis glycosidic bonds, ranging from disaccharides to dodecasaccharides, using a highly efficient preactivation-based one-pot glycosylation strategy. This library includes compounds with various sulfation patterns (2,3-O-di-, 3,4-O-di-, and 2,3,4-O-tri-sulfation) encompassing nearly all possible fucoidan structures. In vitro anticoagulant assays demonstrate that both molecular size and degree of sulfation play crucial roles in anticoagulant potency. Notably, compounds 29, 30, 37, and 58 significantly prolong human plasma activated partial thromboplastin time (APTT), comparable to the effect of enoxaparin, without affecting prothrombin time (PT) or thrombin time (TT). This selective inhibition of the intrinsic coagulation pathway suggests a reduced risk of bleeding, highlighting the therapeutic potential of these fucoidans as safer anticoagulant agents. Fucoidan is a sulfated glycan with anticoagulant properties, but its structural complexity and heterogeneity hinders understanding of its structure-activity relationship. Here, the authors synthesize a diverse library of 58 distinct fucoidans with multiple contiguous 1,2-cis glycosidic bonds and various sulfation patterns, and investigate their anticoagulant activity.

  • Stereochemistry Drives the Macromolecular Conformation and Biological Activity of Glycopolymers

    ACS Central Science · 2025-08-06 · 4 citations

    articleOpen accessSenior authorCorresponding

    Chirality plays a fundamental role in biology, where stereochemical information governs how molecules fold, interact, and function. While the effects of stereochemistry are well-established for small molecules and natural biomacromolecules, less is known about how it shapes the properties of synthetic, biomimetic polymers. In this study, we explore how backbone and glycan stereochemistry influences conformation, physical interactions, and biological behavior in water-soluble glycopolymers. Using ring opening metathesis polymerization (ROMP), we synthesized precision glycopolymers (PGPs) from two diastereomeric norbornenyl moieties (endo and exo) and monosaccharides (glucose, galactose, and mannose). Despite having nearly identical molecular and macromolecular compositions, the resulting PGPs displayed major differences in their physical and biological properties. Glycopolymers with β-linkages showed distinct circular dichroism (CD) signals, and exo-derived backbones displayed more hydrophobic local environments, as confirmed by all-atom molecular dynamics simulations and dye interaction studies. These structural differences had clear functional consequences. exo-PGPs bound plant lectins more rapidly and with higher avidity, whereas endo-PGPs showed greater selectivity toward human galectin-3, stronger inhibition of cholera toxin, and enhanced uptake into 4T1 triple-negative breast cancer cells. Together, these findings provide the first demonstration of biological activity in endo-derived glycopolymers and establish backbone stereochemistry as a key design element that encodes macromolecular behavior in biologically relevant contexts.

  • Injectable and self-healing fucoidan hydrogel: A natural anti-inflammatory biomaterial

    Biomaterials · 2025-08-23 · 7 citations

    article
  • Systematic Evaluation of Macromolecular Carbohydrate-Lectin Recognition Using Precision Glycopolymers

    Biomacromolecules · 2024-11-06 · 13 citations

    articleSenior authorCorresponding

    The precise modulation of protein-carbohydrate interactions is critical in glycobiology, where multivalent binding governs key cellular processes. As such, synthetic glycopolymers are useful for probing these interactions. Herein, we developed precision glycopolymers (PGPs) with unambiguous local chemical composition and well-defined global structure and systematically evaluated the effect of polymer length, hydrophobicity, and backbone hybridization as well as glycan density and identity on the binding to both mammalian and plant lectins. Our studies identified glycan density as a critical factor, with PGPs below 50% grafting density showing significantly weaker lectin interactions. Coarse-grained molecular dynamics simulations suggest that the observed phenomena may be due to a decrease in carbohydrate-carbohydrate interactions in fully grafted PGPs, leading to improved solvent accessibility. In functional assays, these PGPs reduced the cell viability and migration in 4T1 breast cancer cells. Our findings establish a structure-activity relationship in glycopolymers, providing new strategies for designing synthetic glycomacromolecules for a myriad of applications.

Frequent coauthors

Education

  • Ph.D., Chemistry

    University of California San Diego

    2018
  • M.S., Chemistry

    University of California San Diego

    2014
  • B.S., Biochemistry

    West Chester University

    2012

Awards & honors

  • Outstanding Dissertation Award from the UC San Diego Departm…
  • Inamori Foundation Fellowship
  • ARCS Foundation Fellowship
  • Cancer Researchers in Nanotechnology program (NIH R25T) Fell…
  • American Cancer Society Postdoctoral Fellowship
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