Education

B.S. (Chemistry and Mathematics) 1968, Davis and Elkins College

Ph.D. (Physical Chemistry) 1972, University of Delaware, Newark

Research Summary

1) One of our research interests centers around studying at atomic resolution the structural and functional properties that define molecular recognition systems that activate and regulate biological properties. In particular, we study the energetics of hormone-induced receptor activation and regulation of growth hormone and its receptor using X-ray crystallography, site-directed mutagenesis, phage display mutagenesis and biophysical analysis.

2) Synthetic Antibodies- We use novel phage display libraries and screening procedures to produce a new class of synthetic affinity binders (sABs) based on Fab antibody scaffolds. These synthetic antibodies are much more versatile than traditional monoclonal antibodies and can be tuned to bind to multi-protein complexes and specific conformational states of their protein targets. These attributes make them the reagents of choice to study complex processes like cell signaling and cytokinesis.

3) Drug delivery- We have developed a unique drug delivery method that utilizes ligand-induced receptor-mediated endocytosis pathways. We call this method Receptor-Mediated Delivery (RMD) and have shown that we can deliver functionally active proteins and RNA/DNA cargoes into live cells for functional and imaging experiments.

4) Synthetic biology- We use a combination of peptide synthesis and phage display (biosynthetic phage display) to produce proteins with novel properties.

Selected Publications

K29-linked ubiquitin signaling regulates proteotoxic stress response and cell cycle
Yuanyuan Yu, Qingyun Zheng, Satchal K. Erramilli, Man Pan, Seongjin Park, Yuan Xie, Jingxian Li, Jingyi Fei, Anthony A. Kossiakoff, Lei Liu & Minglei Zhao. Nat Chem Biol. 2021 Jul 8. doi: 10.1038/s41589-021-00823-5 PMID: 34239127

A T cell redirection platform for co-targeting dual antigens on solid tumors
Leonie Enderle, Karim H Shalaby, Maryna Gorelik, Alexander Weiss, Levi L Blazer, Marcin Paduch, Lia Cardarelli, Anthony Kossiakoff, Jarrett J Adams, Sachdev S Sidhu MAbs. Jan-Dec 2021;13(1):1933690. doi: 10.1080/19420862.2021.1933690 PMID: 34190031

Structural basis of omega-3 fatty acid transport across the blood-brain barrier
Rosemary J Cater, Geok Lin Chua, Satchal K Erramilli, James E Keener, Brendon C Choy, Piotr Tokarz, Cheen Fei Chin, Debra Q Y Quek, Brian Kloss, Joseph G Pepe, Giacomo Parisi, Bernice H Wong, Oliver B Clarke, Michael T Marty, Anthony A Kossiakoff, George Khelashvili, David L Silver, Filippo ManciaNature volume 595, pages315–319 (2021)

Inhibition of Cancer Cell Adhesion, Migration and Proliferation by a Bispecific Antibody that Targets two Distinct Epitopes on αv Integrins
Gallo E, Kelil A, Haughey M, Cazares-Olivera M, Yates BP, Zhang M, Wang NY, Blazer L, Carderelli L, Adams JJ, Kossiakoff AA, Wells JA, Xie W, Sidhu SS J Mol Biol. 2021 Jun 4;433(15):167090. doi: 10.1016/j.jmb.2021.167090. PMID: 34090922

Engineered ultra-high affinity synthetic antibodies for SARS-CoV-2 neutralization and detection
Slezak T, Kossiakoff AA J Mol Biol. 2021 Mar 25;doi: 10.1016/j.jmb.2021.166956. PMID: 33775667

2020

Recognition of an α-helical hairpin in P22 large terminase by a synthetic antibody fragment
Lokareddy RK, Ko YH, Hong N, Doll SG, Paduch M, Niederweis M, Kossiakoff AA, Cingolani G Acta Crystallogr D Struct Biol. 2020 Sep 1;76(Pt 9):876-888. PMID: 32876063

Structure of human Frizzled5 by fiducial-assisted cryo-EM supports a heterodimeric mechanism of canonical Wnt signaling
Tsutsumi N, Mukherjee S, Waghray D, Janda CY, Jude KM, Miao Y, Burg JS, Aduri NG, Kossiakoff AA, Gati C, Garcia KC. Elife. 2020 Aug 7;9:e58464. PMID: 32762848

Synthetic antibodies against BRIL as universal fiducial marks for single-particle cryoEM structure determination of membrane proteins
Mukherjee S, Erramilli SK, Ammirati M, Alvarez FJD, Fennell KF, Purdy MD, Skrobek BM, Radziwon K, Coukos J, Kang Y, Dutka P, Gao X, Qiu X, Yeager M, Eric Xu H, Han S, Kossiakoff AA Nat Commun 2020 Mar;11(1):1598 PMID: 32221310

Structure and mechanism of the ER-based glucosyltransferase ALG6
Bloch JS, Pesciullesi G, Boilevin J, Nosol K, Irobalieva RN, Darbre T, Aebi M, Kossiakoff AA, Reymond JL, Locher KP Nature 2020 03;579(7799):443-447 PMID: 32103179

Structure and drug resistance of the Plasmodium falciparum transporter PfCRT
Kim J, Tan YZ, Wicht KJ, Erramilli SK, Dhingra SK, Okombo J, Vendome J, Hagenah LM, Giacometti SI, Warren AL, Nosol K, Roepe PD, Potter CS, Carragher B, Kossiakoff AA, Quick M, Fidock DA, Mancia F Nature 2019 Nov; PMID: 31776516