Summary

Dr. Schwendeman’s long-term research goal is to design highly potent and safe synthetic high-density lipoprotein (HDL) nanomedicines for treatment of atherosclerosis. These 10 nm size particles mimic the natural HDL function of cholesterol removal from arterial plaques and subsequent cholesterol transport to the liver for elimination. Dr. Schwendeman spent 12 years in pharmaceutical industry at Cerenis Therapeutics (Fierce 15 biotech, www.cerenis.com), Pfizer, and Esperion Therapeutics. She was involved in discovery and translation of several HDL therapies to Phase II clinical trials. Her efforts led to development of a kilo-scale recombinant Apolipoprotein A-I process and highly homogeneous and safe HDL particles for the largest-to-date Phase II sHDL clinical trial (>500 patients). She successfully submitted FDA INDs for six different products including nanoparticles, liposome, proteins, peptides and small molecules.

 

Her current research interests focus on understanding the mechanisms of how phospholipid composition of HDL affects its potency, and designing short synthetic peptides that mimic various functions of Apolipoprotein A-I, the main protein component of HDL. Her laboratory has several ongoing translational collaborative projects focused on assessing sHDL utility for treatment of Alzheimer's disease, sepsis, acute lung injury, lupus and diabetic nephropathy.  Dr. Schwendeman also explores the utility of these “nature-made” nanoparticles for targeted delivery of chemotherapeutics to SR-BI (HDL-receptor)-expressing tumors as well as for delivery of peptide antigens. Finally, her laboratory is active in developing science-based regulations for testing of complex parenteral products such as nanoparticles, recombinant proteins and microspheres. Research is currently supported by grants from the American Heart Association and the US Food and Drug Administration.

Research Interests

  • Rational design of novel synthetic HDL nanomedicines for treatment of atherosclerosis by designing new ApoA-I mimic peptides and optimizing phospholipid composition

  • Therapeutic applications of HDL nanomedicines for treatment of Alzheimer’s disease, septic shock, acute lung injury, lupus and diabetic nephropathy

  • Natural HDL nanocarriers for targeted delivery of anticancer drugs, miRNA and peptide antigen to infected cells overexpressing SR-BI receptor

  • Regulatory science; establishing characterization methods for complex parenteral drugs predictive of in vivo performance to aid development of FDA regulatory guidelines

  • Establishing regulatory framework for predicting in vivo performance of complex parenteral drugs based on analytical characterization in vitro

Awards

  • 2015 Winner of Biomedical Innovation Shark Tank

Selected Publications

  • Busseuil, D, Merlet, N., Avram-Mihalache, T., Mecteau, M., Shi, Y.-F., Brand, G., Nachar, W., Sy, G., Schwendeman, A., Lalwani, N., Dasseux, J.-L., and Tardif, J.-C., HDL mimetic peptide CER-522 treatment regresses left ventricular diastolic dysfunction in an aortic valve stenosis model, submitted to British J. of Pharmacology (2013).

  • Schwendeman, A., Sviridov, D., Yuan, Y., Stonik, J., Ossoli, A., Thacker, S., Pryor, M., O'Mahony, A., Polokoff, M., Killion, S., Turner, S. and Remaley, A. T., Lipid composition of rHDL determines cholesterol efflux in vitro and in vivo, submitted to J. Lipid Research (2013).

  • Zhong, Y., Ding, A., Zhang, L., Shenderova, A., Zhu, G., Pei, P., Chen, R., Mallery, S. R., Mooney, D. J. and Schwendeman, S. P., Rescue of SCID murine ischemic hindlimbs with pH-modified rhbFGF/poly(D,L-lactic-co-glycolic acid) implants, J. Controlled Release, 122, 331-337 (2007).

  • Ding, A. G., Shenderova, A. and Schwendeman, S. P., Prediction of microclimate pH in poly(lactic-co-glycolic acid) films, J. Am. Chem. Soc., 128, 5384-5390 (2006).

  • Shenderova, A., Ding, A. G. and Schwendeman, S. P., Potentiometric method for determination of microclimate pH in poly(lactic-co-glycolic acid) films, Macromolecules, 37, 10052-10058 (2004).

Recent Publications

  • Carolyne K. Smith; Nickie L. Seto; Anuradha Vivekanandan-Giri; Wenmin Yuan; Martin P. Playford; Zerai Manna; Sarfaraz A. Hasni; Rui Kuai; Nehal N. Mehta; Anna Schwendeman; Subramaniam Pennathur; Mariana J. Kaplan Lupus high-density lipoprotein induces proinflammatory responses in macrophages by binding lectin-like oxidised low-density lipoprotein receptor 1 and failing to promote activating transcription factor 3 activity. Annals of the Rheumatic Diseases. 2016;():
  • Matthew J. Taylor; Aalok R. Sanjanwala; Emily E. Morin; Elizabeth Rowland-Fisher; Kyle Anderson; Anna Schwendeman; William E. Rainey Synthetic High-Density Lipoprotein (sHDL) inhibits steroid production in HAC15 adrenal cells. Endocrinology. 2016;157(8):3122-3129
  • Wenmin Yuan; Rui Kuai; Zhipeng Dai; Yue Yuan; Nan Zheng; Wenlei Jiang; Charles Noble; Mark Hayes; Francis C. Szoka; Anna Schwendeman Development of a Flow-Through USP-4 Apparatus Drug Release Assay to Evaluate Doxorubicin Liposomes. AAPS Journal. 2016;():1-11
  • Meng Zhang; Rui Huang; Rose Ackermann; Sang Choul Im; Lucy Waskell; Anna Schwendeman; Ayyalusamy Ramamoorthy Reconstitution of the Cytb5-CytP450 Complex in Nanodiscs for Structural Studies using NMR Spectroscopy. Angewandte Chemie - International Edition. 2016;():
  • Rui Kuai; Dan Li; Y. Eugene Chen; James J. Moon; Anna Schwendeman High-Density Lipoproteins. ACS Nano. 2016;10(3):3015-3041