Partha Sampathkumar Email & Phone Number

South San Francisco, California, United States

California, United States

• Produced several “difficult to express and purify” proteins (at 1- to 10- liter scale) with low endo-toxin for in vivo immunization campaigns and structural studies. • Proficiently applied AKTA systems for protein purification process development using affinity (ProA, His-tag, and Strep-tag), ion-exchange, size-exclusion, ceramic hydroxyapatite, and hydrophobic chromatography methods.• Received “Upside-Down” and “Figure 8” awards at Surrozen.• Lead author in a manuscript (soon to be submitted) highlighting the structure and function of Surrozen’s SWEETS molecules as antibody-based PROTACs that function as a Targeted Protein Degradation system via AbTAC and LYTAC dual mechanisms to enhance Wnt signaling in hepatocytes to treat liver diseases.• Led generation of Developability Data Package that were critical to selection of Surrozen’s clinical candidates SZN-413, SZN-043, and SZN-1326 for Retinal, Liver, and Intestinal diseases.• Led and performed Developability assays for Biologics including thermal stability, HIC, computational sequence- and structure-based Manufacturability assessments, Forced-degradation, AAPH-oxidation stress, low pH-hold, freeze-thaw, storage stability assays with end points including SE-HPLC, RP-HPLC, CE-SDS, cIEF, BLI, Mass-spectrometry, and cell-based activity assays, poly-reactivity ELISA and serum-compatibility investigation. Authored and reviewed SOPs for above assays.• Generated, analyzed, assembled, and presented data in high-level discussions including Scientific Advisory Board (SAB) and Business development meetings. Developability data on SZN-413 was a critical component of overall data package that led to the Surrozen - Boehringer Ingelheim partnership in Retinal diseases.• Actively made critical contribution to project teams including CMC production of SZN-043 and SZN-1326 in Surrozen-Lonza partnership, Kidney and Cornea diseases. Led discussions with several KOLs for Surrozen's Kidney and Developability programs.

San Francisco Bay Area

• Determined ~20 crystal structures of antigen-Fab complexes for epitope mapping, structure activity relationships (SAR) and analyzed structures for protein engineering and development of biologics. • Patent: WO2019126399 - ANTI-FRIZZLED ANTIBODIES AND METHODS OF USE • Patent: WO2019126401 - ANTI-LRP5/6 ANTIBODIES AND METHODS OF USE • Patent: WO2020132356 - ANTIGEN BINDING FORMATS FOR RECEPTOR COMPLEXES • Patent: WO2021003416 - MONOSPECIFIC ANTI-FRIZZLED ANTIBODIES AND METHODS OF USE • Patent: WO2022192445 - MODULATION OF WNT SIGNALING IN GASTROINTESTINAL DISORDERS

San Francisco Bay Area

New York Ny

• Purification, crystallization, and structure determination of human Jak2 pseudokinase domain with small-molecule ligands, and expression of full-length and 3-doamin human Jak2 in Baculovirus-insect cell system. Publication:Virtanen AT, Haikarainen T, Sampathkumar P, Palmroth M, Liukkonen S, Liu J, Nekhotiaeva N, Hubbard SR, Silvennoinen O (2023). Identification of novel small molecule ligands for JAK2 pseudokinase domain. Pharmaceuticals 16(1), 75. https://doi.org/10.3390/ph16010075

New York, Ny

• Extensively applied baculovirus / insect-cell system for expression of a human kinase towards purification, characterization, and crystallization trails.• Transiently expressed kinase mutants in HEK293 cells in 96-well format and characterized their expression and activation using western blot analyses.• Performed gene cloning, small-scale expression testing, large-scale protein production, crystallization screens, and crystal-growth optimization using high-throughput techniques.• Guided associate scientists in day-to-day laboratory research and involved in project management.

Greater New York City Area

• The Nuclear Pore Complex, composed of proteins called Nucleoporins (Nups), mediates the nucleo-cytoplasmic transport of macromolecules in eukaryotes. Determined the structure of a 110 kDa N-terminal domain S. cerevisiae Nup192 (~1000 residues in the asymmetric unit and 3.25Å resolution), a protein recalcitrant towards crystallization, which represents an important mile-stone towards structural understanding of NPC function. This work was high-lighted on the cover of April 2, 2013 issue of the journal Structure and also in http://sbkb.org/fs/piecing-together-the-nuclear-pore-complex.• Determined the high-resolution structure of mouse CD27, a Tumor Necrosis Factor (TNF) receptor, by Sulfur-phasing, and currently working towards structure determination of CD27 with its TNF-ligand CD70.• Successfully refolded mouse and human Leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1; a collagen receptor), and determined their high-resolution crystal structures by SeMET-SAD phasing.Publications:1. Sampathkumar P, et al., (2013). Structure, Dynamics, Evolution and Function of a Major Scaffold Component in the Nuclear Pore Complex. Structure 21, 560-571. http://dx.doi.org/10.1016/j.str.2013.02.0052. Kim SJ, Fernandez-Martinez J, Sampathkumar P, et al., (2014). Integrative Structure-Function Mapping of the Nucleoporin Nup133 Suggests a Conserved Mechanism for Membrane Anchoring of the Nuclear Pore Complex. Mol. and Cell. Proteomics.http://dx.doi.org/10.1074/mcp.M114.0409153. Soniat M, Sampathkumar P, et al., (2013) Crystal structure of human Karyopherinβ2 bound to the PY-NLS of Saccharomyces cerevisiae Nab2 . J Struct Funct Genomics DOI 10.1007/s10969-013-9150-1.4. Sampathkumar P*, et al., (2012). Atomic structure of the Nuclear Pore Complex targeting domain of a Nup116 homologue from the yeast, Candida glabrata. Proteins:Structure, Function, and Bioinformatics 80, 2010-2116.

San Diego Ca

• PHR proteins play a critical role in synaptogenesis and axon guidance. PHR domains are essential for proper localization of PHR proteins. Determined first high-resolution crystal structures PHR domains of Mouse Phr-1, and established inter-institutional collaborations to explain a loss of function mutation via structural principles.• Determined and analyzed the crystal structure of an integral membrane protein BenF-like porin from Pseudomonas fluorescens.• Obtained hands-on experience in purification, characterization, and setting up lipidic cubic phase (LCP) crystallization of membrane proteins.• Performed Construct Design using a variety of bioinformatics tools, and high-throughput molecular cloning, expression, and purification of several proteins.• Contributed towards structure determination of several Protein Structure Initiative project targets, and played a leadership role in writing and communicating research papers to scientific journals as corresponding author.Publications:1. Sampathkumar P*, et al., (2010). Structures of PHR domains from Mus musculus Phr1, explain the loss of function mutation of the C. elegans homolog RPM-1. J. Mol. Biol. 397, 883-892http://dx.doi.org/10.1016/j.jmb.2010.02.0172. Sampathkumar P*, et al., (2010). Structure of a putative BenF-like porin from Pseudomonas fluorescens Pf-5 at 2.6 Å resolution. Proteins: Structure, Function and Bioinformatics 78, 3056-3062.http://www.ncbi.nlm.nih.gov/pubmed/207374373. Sampathkumar P*, et al., (2010). Structure of the autoproteolytic domain from the nuclear pore complex component NUP145 from Saccharomyces cerevisiae. Proteins: Structure, Function, and Bioinformatics 78, 1992-1998.http://www.ncbi.nlm.nih.gov/pubmed/203100664. Sampathkumar P *, et al., (2011). Structure of the C-terminal domain of NUP133, a component of the yeast Nuclear Pore Complex. Proteins: Structure, Function and Bioinformatics 79, 1672-1677.http://www.ncbi.nlm.nih.gov/pubmed/21365675

• PHR proteins play a critical role in synaptogenesis and axon guidance. PHR domains are essential for proper localization of PHR proteins. Determined first high-resolution crystal structures PHR domains of Mouse Phr-1 and established inter-institutional collaborations to explain a loss of function mutation via structural principles.• Determined and analyzed the crystal structure of an integral membrane protein BenF-like porin from Pseudomonas fluorescens.• Hands-on experience in purification and lipidic cubic phase (LCP) crystallization of membrane proteins.• Performed Construct Design using a variety of bioinformatics tools, and high-throughput molecular cloning, expression, and purification of several proteins.• Contributed towards structure determination of several Protein Structure Initiative project targets and played a leadership role in writing and communicating research papers to scientific journals as corresponding author.Publications: Sampathkumar P * et al., (2010). Structures of PHR domains from Mus musculus Phr1, explain the loss of function mutation of the C. elegans homolog RPM-1. J. Mol. Biol. 397, 883-892. http://www.ncbi.nlm.nih.gov/pubmed/20156452 Sampathkumar P * et al., (2010). X-ray structure of a BenF-like porin from Pseudomonas fluorescens Pf-5 reveals the signature of aromatic acid selectivity filters. Proteins: Structure, Function and Bioinformatics 78, 3056-3062. http://www.ncbi.nlm.nih.gov/pubmed/20737437 Sampathkumar P *, et al., (2010). Structure of the autoproteolytic domain from the nuclear pore complex component NUP145 from Saccharomyces cerevisiae. Proteins: Structure, Function, and Bioinformatics 78, 1992-1998. http://www.ncbi.nlm.nih.gov/pubmed/20310066 Sampathkumar P * et al (2012). Atomic structure of the Nuclear Pore Complex targeting domain of a Nup116 homologue from the yeast, Candida glabrata. Proteins:Structure, Function, and Bioinformatics 80, 2010-2116. http://www.ncbi.nlm.nih.gov/pubmed/22544723

Peroxins (PEX) from Trypanosoma brucei:• Successfully crystallized the Peroxisomal Targeting Signal 1 (PTS1) binding domain of Trypanosoma brucei PEX5, a potential drug target, by extensively application of Surface Entropy Reduction mutagenesis.• Determined crystal structures of T. brucei PEX5 in complex with five different PTS1 peptides, thereby identifying a unique hydrophobic pocket in the subdomain interface that represents an attractive inhibitor binding site to prevent relative motions of the subdomains.Flavin Dependent Thymidylate Synthase (FDTS, ThyX) from Mycobacterium tuberculosis:• Determined the crystal structure of Mycobacterium tuberculosis ThyX (~2000 residues in the asymmetric unit), a potential drug target responsible for synthesis of thymidine, in the presence of the co-factor FAD and a substrate-analog (ternary complex). Structural analyses provided mechanistic insights into ThyX catalysis.• Determined structure of MtbThyX-NADP+ complex and obtained insights to design bi-functional inhibitors.Publications:1. Sampathkumar P, Roach C, Michels PAM and Hol WGJ (2008). Structural insights into recognition of the Peroxisomal Targeting Signal 1 by the PTS1 binding domain of Trypanosoma brucei Peroxin 5. J. Mol. Biol. 381, 867-880http://dx.doi.org/10.1016/j.jmb.2008.05.08 2. Sampathkumar P, Turley S, Ulmer JE, Rhie HG, Sibley CH and Hol WGJ (2005). Structure of the Mycobacterium tuberculosis Flavin dependent Thymidylate Synthase (Mtb ThyX) at 2.0 Å Resolution. J. Mol. Biol. 352, 1091-1104http://dx.doi.org/10.1016/j.jmb.2005.07.0713. Sampathkumar P, Turley S, Sibley CH and Hol WGJ (2006). NADP+ expels both the Co-factor and a substrate analog from the Mycobacterium tuberculosis ThyX active site: opportunities for anti-bacterial drug design. J. Mol. Biol. 360, 1-6http://dx.doi.org/10.1016/j.jmb.2006.04.061

Ph.D., Biophysics, Structural Biology

Activities and Societies: • Received all India Rank 3 (score of 99.81 percentile) in the Graduate Aptitude Test in Engineering.

Master Of Science (M.Sc.), Chemistry, First Class With Distinction (Gold Medal)

Bachelor Of Science (B.Sc.), Chemistry, Physics, And Mathematics, First Class