Speakers
Keynote Speakers
Prof. Abhishek Chatterjee | Boston College
Abhishek Chatterjee is a Professor in the Department of Chemistry at Boston College. The Chatterjee lab combines directed evolution and genetically encoded new-to-nature chemistries to develop tools for probing complex biological questions and to develop next-generation biotherapeutics. Prior to Boston College, Abhishek received his B.Sc. from the University of Calcutta and M.Sc. from the Indian Institute of Technology (IIT) Kharagpur, completed his PhD at Cornell University (2009), and pursued postdoctoral studies with Professor Peter G. Schultz at The Scripps Research Institute. His research program has been recognized by the Smith Family Award for Excellence in Biomedical Sciences, the Camille Dreyfus Teacher-Scholar Award, the Allen Distinguished Investigator Award, the Bioconjugate Chemistry Young Investigator Award and the Ono Pharma Breakthrough Science Initiative Award.
Dr. Ingo Mügge | Alkermes
Dr. Ingo Mügge is an Alkermes Fellow and Head of Modeling and Informatics at Alkermes in Waltham, Massachusetts, where he leads computational efforts supporting the discovery and development of innovative medicines for neurological and psychiatric disorders. His research interests span drug design, predictive modeling, cheminformatics, bioinformatics, and the application of artificial intelligence to enhance R&D productivity and decision-making. Prior to joining Alkermes, Dr. Mügge held a variety of scientific and leadership roles in drug discovery at Boehringer Ingelheim and Bayer Healthcare. He earned a diploma in Physics from Humboldt University of Berlin and a Dr. rer. nat. degree in Computational Chemistry from the Free University of Berlin, followed by postdoctoral research at the University of Southern California in the laboratory of Professor Arieh Warshel and at Abbott Laboratories in the group of Dr. Yvonne Martin. Over a career spanning more than 25 years, Dr. Mügge has contributed to research programs across multiple therapeutic areas, including oncology, cardiometabolic disease, immunology, and neuroscience. He is an author or inventor on more than 100 scientific publications and patents. Most recently, he contributed to the discovery of a portfolio of selective orexin 2 receptor agonists, including alixorexton, ALKS 4510, and ALKS 7290, helping expand the therapeutic potential of orexin biology beyond disorders of sleep and wakefulness into attention, fatigue, and other neuropsychiatric symptom domains.
Academic Morning Session Chair
Dr. Danny Thach | Massachusetts Institute of Technology
Danny Thach is an incoming Assistant Professor in the Department of Chemistry at the Massachusetts Institute of Technology. He obtained his BA in Chemistry from the University of Texas at Austin in 2016, then earned his PhD with Professor Thomas Maimone at the University of California, Berkeley (2022), and completed postdoctoral studies with Professor Robert Knowles at Princeton University (2026). At MIT, research in the Thach lab will focus on methodology development and natural product total synthesis.
Student/Postdoc Speakers
Dr. Alina Ringaci | Grinstaff Group, Boston University
A Coiled-Coil Peptide Zipper to Create Antibody–Drug Conjugates
Antibody–drug conjugates (ADCs) are effective cancer therapeutics, but conventional formulations often suffer from heterogeneity, instability, and inconsistent drug loading that compromise clinical performance. To address these limitations, we developed a plug-and-play bioconjugation platform utilizing supramolecular assembly of coiled-coil peptides. This modular strategy enables site-specific, stoichiometric attachment of diverse functional payloads including small molecules, enzymes, or nucleic acids without compromising antibody function. In vivo, a monomethyl auristatin E–loaded conjugate significantly reduced tumor volume compared to antibody monotherapy, demonstrating competitive efficacy against a best-in-class control. Overall, this versatile platform provides a straightforward route to stable, homogeneous antibody conjugates for diverse cancer interventions.
Dr. Ming Zhang | Niu Group, Boston College
C-Polysaccharides via Stereoselective Radical Ring-Opening Polymerization of Minimally Protected Monosaccharides
Polysaccharides are widely used in biomedical applications because of their good biocompatibility and diverse biological functions. However, obtaining sufficient quantities of structurally well-defined natural polysaccharides remains challenging, and their broader applications can also be limited by variations in solubility, susceptibility to enzymatic degradation, and difficulties in functionalization. Here, we report a new vinyl cyclopropane glycoside monomer and its radical ring-opening polymerization to construct C-polysaccharide featuring a unique 1,3-linked architecture and a stable all-carbon backbone. Notably, the polymerization proceeds without hydroxyl protection, exhibits good stereoselectivity, and enables controlled molecular weights with relatively narrow molecular weight distributions. The polymerization can be carried out through a facile and potentially scalable aqueous process, while further post-polymerization functionalization affords a series of highly water-soluble derivatives. This approach provides a new platform for constructing structurally well-defined, functionally tunable carbohydrate-inspired polymers with enzymatic stability and demonstrates their potential for biomedical applications.
Maxwell Sykes | Bennet Group, Tufts University
Studies Towards the Oligosaccharide of Pyridapeptide E
Ever since the advent of vancomycin in modern medicine, glycopeptides have garnered particular attention for their potent anti-microbial and cytotoxic effects in a world where drug-resistant strains of pathogens are becoming a real concern. In recent years, the structural elucidation and subsequent SAR assays of the Pyridapeptide (A-E) glycopeptide series have bolstered our Lab’s personal interest in the oligosaccharide moiety present on Pyridapeptide E, in particular. Coupling our longstanding interest in deoxy sugars and their clear conferring of anti-microbial activity, we set forth to explore the total synthesis of the tetrasaccharide found in Pyridapeptide E. Furthermore, we will conduct subsequent structure-activity-relationship studies on the oligosaccharide motif with the goal of assessing its therapeutic properties, all-the-while showcasing our Lab’s means for the direct, stereoselective formation of beta-linked glycosylation products.
Zixiang Jiang | Xu Group, Brandeis University
Iron-catalyzed highly stereoselective glycosylation methods in rapid synthesis of heparan sulfate oligosaccharides and Fondaparinux
Complex carbohydrates are directly involved in essential life processes; however, their structural complexity and limited availability in homogeneous forms represent a major roadblock that hampers study of their important biological functions. Therefore, pursuing broadly effective and highly stereoselective chemical glycosylation methods are urgently needed. In this talk, an iron-catalyzed 1,2-cis selective glycal aminoglycosylation and an iron-catalyzed stereospecific glycosylation with glycal epoxides recently developed in Hao Xu lab will be introduced. Those 2 methods are nicely utilized in the assembly of heparan sulfate oligosaccharides and Fondaparinux, which are key anticoagulant medicines and intrinsically very hard to synthesize. Every glycosidic linkage in heparan sulfate oligosaccharides and Fondaparinux can be assembled by one of these iron-catalyzed, entirely stereoselective glycosylation reactions. Their syntheses will also be discussed.
Alexander Mueller | Elkin Group, Massachusetts Institute of Technology
Site-Selective Insertion of Amino Acids into Amide Bonds Enabled by N-Nitrosation
Peptides and peptidomimetics are important therapeutic modalities, yet the direct post-synthetic modification of their amide backbones remains challenging. The ability to insert molecular fragments into amide bonds could substantially expand the structural and chemical space accessible from existing peptide and amide scaffolds without requiring their de novo synthesis. Here, we present a general strategy for the site-selective insertion of amino acid fragments into amide bonds through N-nitrosamide activation. The reaction accommodates the insertion of canonical amino acids, non-canonical amino acids, and peptide fragments into peptides, pharmaceutical derivatives, and macrocycles. Preferential N-nitrosation of the most sterically accessible and electron-rich amide enables the site-selective modification of a single amide group within polyamide substrates, and a 2-feature model predicts the site of nitrosation with 85% accuracy. Together, this approach enables the rapid conversion of readily available amides and peptides into a wide range of diversified depsipeptides and peptidomimetics.
Vinou Val | Ferrins Group, Northeastern University
Optimization of pyrazolopyridine derivatives as inhibitors of Trypanosoma brucei
Human African trypanosomiasis (HAT) is a neglected tropical disease caused by the parasite Trypanosoma brucei. There are two subspecies, T. brucei gambiense and T. brucei rhodesiense, responsible for chronic and acute infections in humans, respectively. Current treatments are ineffective, associated with toxicity, or complex administration. Fexinidazole was recently approved and is currently the only oral treatment, though it is only approved to treat T.b. gambiense infections, and ~10% of patients experience parasite recurrence within 18 months. New treatments such as acoziborole, at present in clinical trials, are still needed in case of failure of current treatments and parasitic resistance. A high-throughput screen of kinase inhibitor chemotypes identified the pyrazolopyridine scaffold as a potent T. brucei parasite growth inhibitor. These compounds are known HsGSK3β inhibitors, and a parasite hop to TbGSK3β was hypothesized. This target is highly homologous to human kinases HsGSK3a/β, therefore selectivity was a key part of our optimization strategy. We have used structurebased drug design and differences in the active site of TbGSK3β and HsGSK3β to influence modifications that improve solubility and potency. Improving the solubility of the scaffold has been explored through modifications of the solvent exposed region and a reduction in planarity. Additionally, we investigated structure-activity relationships (SAR) using Topliss analysis. To date, we have synthesized 38 new analogs and tested them for activity in T.b. brucei parasite growth assays, TbGSK3β and HsGSK3β inhibition, as well as ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity). Although achieving selectivity and identifying a valid mechanism of action remains a work in progress, we have identified analogs as 11-fold more potent against T.b. brucei and increased solubility 15-40- fold over the starting point.
Julia Morriss | Liau Group, Harvard University
Charting a Sequence–Function Atlas of Polycomb Repressive Complex 2 at Amino Acid Resolution
Chemical-genetic approaches that systematically perturb protein sequence offer a powerful strategy for probing protein function. Base editor scanning extends this strategy to multi-subunit protein complexes, enabling thousands of defined amino acid substitutions to be evaluated in parallel at native stoichiometric and in native cellular contexts. This capability is particularly valuable for epigenetic complexes such as Polycomb Repressive Complex 2 (PRC2), a master regulator of transcriptional silencing frequently mutated in cancer, whose large size, dynamic composition, and complex regulatory mechanisms complicate conventional study. We applied an integrated base editor scanning approach to PRC2, generating more than 13,000 variants across six subunits using both adenosine and cytidine base editors. By integrating multiple functional and abundance-based readouts, we constructed a high-resolution sequence–function atlas of PRC2 that highlights functional hotspots with potential for therapeutic targeting. Separating effects on protein activity from changes in abundance and integrating these data with complex-level structural analyses identified novel mechanisms governing PRC2 structure and activity, including allosteric regulation at a region of the EZH2–SUZ12 interface that is not fully resolved in existing structures. Applying this approach in an activation-lethality lymphoma model further revealed functional antagonism between PRC2 subcomplexes that shapes the H3K27me3 chromatin landscape. Together, these studies establish a comprehensive sequence–function atlas of PRC2 and demonstrate a generalizable framework for dissecting the function of multi-subunit protein complexes.
Jordan Liles | Coley Group, Massachusetts Institute of Technology
Modeling Reaction Feasibility to Identify New Opportunities for Sigmatropic Rearrangements
Defining the scope and limitations of synthetic methods de-risks synthetic design and sets a clear horizon for method development. Computation can play a central role here if it can anticipate reaction success or failure a priori. In this talk, I will describe reaction feasibility modeling, an approach that pairs a machine-learned interatomic potential with high-throughput prediction of transition-state geometries and barriers for hypothetical reactions. As a proof of concept, we focus on sigmatropic rearrangements. They span a wide range of thermal activation barriers, enable non-obvious retrosynthetic disconnections and the construction of congested C–C bonds, and are well described by electronic structure theory. Benchmarking against reference theory and experimental kinetics shows strong agreement, and retrospective case studies illustrate its utility in synthesis planning. I will then discuss a prospective application of the workflow to identifying and experimentally realizing a methylenation/Claisen sequence toward the natural product (±)-norbrachycoumarin and a degradant of the synthetic cannabinoid UR-144. A coarse-grained kinetic study across ten substrates, seven of which form all-carbon quaternary centers β to a ketone, shows good agreement between computed barriers and experimental outcomes. Together, these results show how feasibility modeling can reveal opportunities to apply existing methods to valuable chemical space.
Samuel Ojeda | Fischer Group, Harvard University
Degron- independent recruitment of KAT2A expands the target space of CRBN molecular glues
Lysine acetyltransferases (KATs) cooperate with oncogenes such as c- Myc, estrogen receptor, and lysine methyltransferase 2A (KMT2A) fusions to sustain malignant programs. Targeting of KAT proteins has shown clinical efficacy; however, achieving homolog selectivity for most KATs remains a major challenge. By extending cereblon (CRBN)–based molecular glues beyond the canonical degron space, we developed an exquisitely selective degrader of KAT2A. Cryo–electron microscopy revealed that CRBN recruits KAT2A independently of a degron; instead, the molecular glue engages a surface-exposed tyrosine, mimicking antibody-like molecular recognition. Selective KAT2A degradation leads to potent ablation of histone H3 lysine 9 acetylation (H3K9Ac), antiproliferative effects in acute myeloid leukemia cell lines, and in vivo efficacy in a patient-derived xenograft model, establishing KAT2A as a targetable vulnerability to treat a wide range of malignancies. More generally, degron-independent recruitment extends the CRBN-targetable proteome