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School of Pharmacy

expertise: Nanomedicine

(Nanotechnology and nanomedicine for disease prevention and treatment)

Swayam Prabha

Courses Taught:

  • PCEUT505
  • PHARMSCI313
  • PCEUT583

Education

  • PhD in Pharmaceutics and Drug Design, University of Nebraska Medical Center
  • MBA in Healthcare Management, Carlson School of Management, University of Minnesota
  • MS in Pharmaceutics, Banaras Hindu University, India

Research Interests:

  • Translational research
  • Ovarian cancer
  • Targeted drug delivery
  • Cell based therapies
  • Nanoengineered stem cells therapeutics

Biography

After completing doctoral studies at the University of Nebraska Medical Center, Prabha joined the pharmaceutical industry and was involved in the development of clinical formulations,. Her current efforts are focused on developing novel drug/gene delivery approaches to fulfill unmet therapeutic needs. Her tenure in the pharmaceutical industry and involvement in the development of clinical formulations, several of which have been successfully approved by the FDA, have enabled a deeper understanding of what it takes to translate ideas and concepts from laboratory into a clinical drug product. She is involved in designing effective cell-based therapies with fewer side effects for lung and ovarian cancers, both diseases with poor survival rates and in urgent need of novel therapeutic approaches. The overall goal of the lab is to improve mesenchymal stem cells (MSC) tumor homing and to fully understand the impact of anticancer drug loading on MSC biology. Current studies show that MSCs nanoengineered to load paclitaxel actively migrate to lung tumors (Patent: 11684638; Targeted delivery system, system components, and methods), where they are retained for several days, and facilitate targeted delivery of the payload and inhibition of tumor growth. She has mentored 9 graduate students (seven PhD and two MS), 12 postdoctoral fellows, 2 research associates, 4 undergraduate students, several high school students and have served on the advisory committees for other graduate students. She currently mentor two postdoctoral fellows and is on the advisory committee of a PhD student. All her previous trainees have continued successful biomedical science careers in academia and industry. She has been a principal investigator or co-investigator for numerous research awards, including federal (e.g., NIH, NCI/SAIC, DOD), national (American Cancer Society, Minnesota Ovarian Cancer Alliance), industrial (Supernus, BRTI) and intramural funding sources.

Selected Publications

https://pubmed.ncbi.nlm.nih.gov/?term=Prabha+S

Jayanth Panyam

Accepting Students to Lab: Yes

Education

  • PhD in Pharmaceutical Sciences, University of Nebraska Medical Center
  • Master of Pharmacy (Pharmaceutics), Banaras Hindu University
  • Bachelor of Pharmacy, Tamil Nadu Dr. M.G.R. Medical University

Research Interests

  • Targeting the premetastatic niche
  • Novel TLR7/8 agonists as anticancer vaccine adjuvants
  • Antibody-drug conjugates

Biography

Drug delivery systems that are in the ~100 nm size range have been of considerable interest in the field of anti-cancer drug delivery. However, the therapeutic benefit of such systems (for example, liposomal doxorubicin – Doxil® and albumin-bound paclitaxel – Abraxane®) have been realized in only a subset of tumor types, and even in these tumors, the survival benefits have been modest. A detailed understanding of the biological fate of delivery systems and, more importantly, in the microenvironment of the target tissue is necessary to further improve treatment efficacy. For several years, our research was focused on investigating the mechanisms of anticancer drug delivery, with emphasis on understanding how various biological factors influence the effectiveness of various delivery approaches. The ultimate goal is to use the knowledge derived from these studies to devise advanced delivery platforms that can be effectively translated to the clinic. More recently, our focus has broadened to include antibody-drug conjugates as a platform technology for targeting cancer cells. Similarly, we now emphasize eliciting body’s own immunological defenses to fighting cancer. Finally, we have begun to understand how primary tumors start programming vascular organs such as lungs and liver to facilitate metastasis. We are now developing strategies to interfere with this premetastatic niche formation. Specific ongoing projects include:

Targeting the premetastatic niche (PMN)

Metastatic disease continues to be the major cause of mortality in patients with most solid tumors. Significant advances have been made in understanding the changes in tumor cells and the tumor microenvironment that eventually result in secondary lesions. Accordingly, much of the current drug discovery efforts are focused on targets in tumor cells or the primary tumor microenvironment. However, fewer attempts have been made to target the changes that occur in secondary organs before and during metastatic colonization. Recent studies show that primary tumors actively program organs such as the lungs and liver to create the PMN. Our group has been working to understand how changes that occur in the PMN can be targeted to prevent metastatic growth. In patients with metastatic tumors, myeloid-derived suppressor cells (MDSCs) are significantly increased in circulation. Similarly, in mouse models, MDSCs increase in circulation and actively home to premetastatic sites. MDSCs promote metastasis by activating dormant tumor cells via pro-inflammatory S100A8/A9 proteins. The goal of this research is to investigate various small molecule inhibitors and novel biologics to interfere with trafficking of MDSCs to the premetastatic niche and signaling via the S100A8/A9 proteins.

Novel TLR7/8 agonists as anticancer vaccine adjuvants

Agonists of toll like receptors (TLRs) are promising anticancer vaccine adjuvants because of their ability to induce proinflammatory cytokines necessary to generate a robust immune response. However, currently available TLR agonists suffer from several limitations including self-regulatory immunosuppression and unfavorable local pharmacokinetics resulting in poor availability within dendritic cells. Further, current TLR agonist-based anticancer vaccines generate a robust cytotoxic CD8 T cell response but not CD4 Th1 helper T cell response, which is critical for inducing effective, long-term antitumor immunity. We are addressing these important challenges through a synergistic combination of drug discovery and drug delivery efforts. Our team has developed a suite of highly substituted imidazoquinolines, which activate TLR7 and/or 8 and induce significantly higher levels of cytokines compared to imiquimod, an FDA approved TLR7 agonist. Our studies show the balance between pro-inflammatory and immunosuppressive cytokines can be tuned through structural modifications. Encapsulation of these novel agonists in acidic pH responsive nanoparticles (NPs) resulted in robust activation of CD4 and CD8 T cells as well as natural killer (NK) cells, leading to a stronger anticancer immune response than free agonist or that encapsulated in non-pH responsive NPs. Importantly, intradermal delivery of NP vaccine using a hollow microneedle platform led to an enhanced Th1 immune response, which is essential for effective induction of long-term antitumor immunity. Our current studies are focused on further optimizing the new agonists for efficient encapsulation in pH responsive NPs, tune the NP properties for improved targeting of dendritic cells following delivery via hollow microneedles, and investigate potentiation of NK cell-mediated antibody-mediated cellular cytotoxicity.

Antibody-drug conjugates targeting HSPG2 (perlecan)

Bladder cancer (BC) is the most common cancer of the urinary tract. Patients with muscle-invasive disease have a 5-year survival rate less than 50%. Treatment methods for advanced BC have not changed for more than 20 years. Our long-term goal is to develop effective therapeutic strategies against metastatic BC. We have recently identified the overexpression of a cell surface protein called perlecan (HSPG2) on BC cells. Gene expression analysis shows that patients with high HSPG2 expression have a significantly lower survival rate compared to those with low HPSG2 expression, pointing to clinical significance of this novel biomarker. In addition, we have developed a monoclonal antibody (AM6) targeting HSPG2. Conjugation of the cytotoxic drug MMAE to AM6 enables effective targeting of BC cells and results in potent tumor cell kill. The objective of this research is to further develop and evaluate the efficacy of AM6-based antibody-drug conjugate (ADC) in cell culture and mouse models of BC. Our studies are also focused on understanding the structural features of AM6 that could impact its therapeutic efficacy. Further, since HSPG2 is overexpressed in many different solid tumors including breast and ovarian cancer as well as in melanoma, we expect that HSPG2-targeted ADC could be of significant therapeutic benefit.

Selected Publications

https://pubmed.ncbi.nlm.nih.gov/?term=panyam%2C+Jayanth&size=20

 

Shijie Cao

Accepting Students to Lab: Yes

Education

  • PhD in Bioengineering, University of Washington
  • Bachelor of Science in Pharmacy, Fudan University

Research Interests

The Cao Lab at the University of Washington is a dynamic and interdisciplinary research group that focuses on two exciting and innovative research directions: mucosal immunoengineering and microbiome pharmaceutics. We aim to develop innovative and translatable tools that can prevent and treat a host of immunological disorders, including allergies, inflammation, and autoimmune diseases, as well as infectious diseases. Currently, our lab is deeply engaged in developing therapeutics that modulate the immune system by specifically targeting the microbiome and its associated metabolites. By leveraging advanced drug delivery tools and microbiome modulation strategies, we aspire to unravel the complex interplay between the microbiome and various organ systems. This will not only expand our scientific understanding but also harness the potential of the microbiome to forge new pathways in improving human health.

Biography

Dr. Cao received his bachelor’s degree in Pharmacy from Fudan University (Shanghai, China) in 2013, and completed his Ph.D. in Bioengineering at the University of Washington in 2018. Following his doctoral studies, he pursued postdoctoral training in Molecular Engineering at the University of Chicago from 2019-2023. In June 2023, Dr. Cao joined the Department of Pharmaceutics as an Assistant Professor.

Selected Publications

https://www.ncbi.nlm.nih.gov/myncbi/shijie.cao.2/bibliography/public/ 

Rodney JY Ho

Accepting Students to Lab: Yes

Websites

TLC-ART Program

WE-REACH Center

Education

  • PhD, University of Tennessee
  • Bachelor of Science, University of California
  • Post-Doctoral Fellow, Stanford University Internal Medicine

Research Interests

Dr. Ho is known for bio-nanotechnology bio-pharmaceutical research and education that enable transformation of basic biomedical discovery into therapeutics. In addition to innovations in targeted and drug combination synchronous delivery, his research focuses on biology and comprehensive approach to treatments of cancer and infectious diseases of pandemic potential. Some topics include (1) Systems approach to drug combination delivery, transport to target tissues and cells related to disease state intended to improve efficacy and safety; (2) Targeted and Long-acting Combination Anti-Retroviral Therapies and organized TLC-ART program intended for maximizing therapeutic impacts on adults and children (3) Drug and lipid or biomaterial interaction studies that enable the engineering and development of long acting and targeted systems that enhance drug potency and safety.

Biography

Dr. Ho is a professor and presidential entrepreneurial fellow of the University of Washington, and holds appointments at the Fred Hutchinson Cancer Research Center. Professor Ho is the founding Executive Director of the Washington Entrepreneurial Research Evaluation and Commercialization Hub (WE-REACH, a NIH designated National Hub). He has served in a number of leadership roles including Assoc Dean for Research and New Initiatives. His current TLC-ART program, built on a collaborative basic and translational research team composed of scientists, physicians, students and post-doc, focuses on developing targeted, drug-combination and long-acting therapeutics for HIV/AIDS and cancer.  Ho is a distinguished leader in pharmaceutical sciences and systems pharmacology with a proven track record of innovation in long-acting and targeted drug combination therapies for AIDS and Cancer. He serves on a number of national and international initiatives relating to Cancer and HIV therapeutics including LEAP leadership team to facilitate development of long-acting therapies for NIH and WHO’s Unitaid. He is an expert on pharmacology and systems approaches to drug targeting and long-acting therapy. His research aims to improve the therapeutic efficacy and safety of viral and cancer drugs, medical diagnostic agents and vaccines. He is an elected member of National Academy of Innovators, elected fellow of the American Association for the Advancement of Science (AAAS) and the American Association of Pharmaceutical Scientists (AAPS). He studies the relationships between drug target distribution and disease development in cancer, AIDS, and neurological disorders. Building on this understanding, he has developed a systems approach to drug delivery and targeting. He is known for his expertise in bio-therapeutics, lipid-drug and -protein interactions, liposomes, drug-combination nanoparticles, pharmacokinetics, and the interplay between tissue targets and drug penetration. His research has led to enhanced HIV, cancer, and pain medication potency and safety. In addition, he has served as an editor of the Journal of Pharmaceutical Sciences and the author of “Biotechnology and Biopharmaceuticals: Transforming Proteins and Genes into Drugs.” He has also received top honors including the Paul Dawson Biotechnology life-time achievement award, Volwiler life-time research achievement award and the AAPS Biotechnology Research achievement, one of the AAPS’s highest recognitions.

Selected Publications

PubMed link

Ho RJY. “Warp-Speed Covid-19 Vaccine Development: Beneficiaries of Maturation in Biopharmaceutical Technologies and Public-Private Partnerships. J Pharm Sci. 2021, 110(2):615-618. PMID: 33212162

Bak A, Ho RJY. “Advancing Cell and Gene Therapeutic Products for Health Impact – Progress on Pharmaceutical Research, Development, Manufacturing and Controls.” J Pharm Sci. 2021, 110(5):1869-1870. PMID: 33189694. 

Perazzolo S, Zhu L, Lin W, Nguyen A, Ho RJY. “Systems and Clinical Pharmacology of COVID-19 Therapeutic Candidates: A Clinical and Translational Medicine Perspective.” J Pharm Sci. 2021, 110:1002-1017. PMID: 33248057

Ho RJY, Gibaldi M. “Biotechnology and Biopharmaceuticals: Transforming proteins and genes into drugs,” John Wiley and Sons, N.Y., 2nd edition 2013.

Gao Y, Kraft JC, Yu D, Ho RJY. “Recent developments of nanotherapeutics for targeted and long-acting, combination HIV chemotherapy.” Eur J Pharm Biopharm. 2019 May;138:75-91. PMID: 29678735.

Mu Q, Yu J, McConnachie LA, Kraft JC, Gao Y, Gulati GK, Ho RJY. “Translation of combination nanodrugs into nanomedicines: lessons learned and future outlook.” J Drug Target. 2018 Jun-Jul;26(5-6):435-447. PMID: 29285948.

Perazzolo S, Shen DD, Ho RJY. Physiologically Based Pharmacokinetic Modeling of 3 HIV Drugs in Combination and the Role of Lymphatic System after Subcutaneous Dosing. Part 2: Model for the Drug-combination Nanoparticles.

J Pharm Sci. 2022, 111(3):825-837. PMID: 34673094

Bak A, Friis KP, Wu Y, Ho RJY. “Translating Cell and Gene Biopharmaceutical Products for Health and Market Impact. Product Scaling From Clinical to Marketplace: Lessons Learned and Future Outlook.” J Pharm Sci. 2019 Oct;108(10):3169-3175. PMID: 31150697.

Kraft JC, McConnachie LA, Koehn J, Kinman L, Sun J, Collier AC, Collins C, Shen DD, Ho RJY. “Mechanism-based pharmacokinetic (MBPK) models describe the complex plasma kinetics of three antiretrovirals delivered by a long-acting anti-HIV drug combination nanoparticle formulation.” J Control Release. 2018 Apr 10;275:229-241. PMID: 29432823.

Kraft JC, McConnachie LA, Koehn J, Kinman L, Collins C, Shen DD, Collier AC, Ho RJY. “Long-acting combination anti-HIV drug suspension enhances and sustains higher drug levels in lymph node cells than in blood cells and plasma.” AIDS. 2017 Mar 27;31(6):765-770. PMID: 28099191.

Mu Q, Yu J, Griffin JI, Wu Y, Zhu L, McConnachie LA, Ho RJY. “Novel drug combination nanoparticles exhibit enhanced plasma exposure and dose-responsive effects on eliminating breast cancer lung metastasis.” PLoS One. 2020 Mar 6;15(3):e0228557. PMID: 32142553

Selen A, Müllertz A, Kesisoglou F, Ho RJY, Cook JA, Dickinson PA, Flanagan T.“Integrated Multi-stakeholder Systems Thinking Strategy: Decision-making with Biopharmaceutics Risk Assessment Roadmap (BioRAM) to Optimize Clinical Performance of Drug Products.” AAPS J. 2020 Jul 27;22(5):97. PMID: 32719954

Ho RJY. “Midyear Commentary on Trends in Drug Delivery and Clinical Translational Medicine: Growth in Biosimilar (Complex Injectable Drug Formulation) Products Within Evolving Collaborative Regulatory Interagency (FDA, FTC, and DOJ) Practices and Enforcement.” J Pharm Sci. 2017 Feb;106(2):471-476.

Kraft JC, Treuting PM, Ho RJY. “Indocyanine green nanoparticles undergo selective lymphatic uptake, distribution and retention and enable detailed mapping of lymph vessels, nodes and abnormalities.” J Drug Targeting. 2018 Jun-Jul;26(5-6):494-504. PMID: 29388438.

Perazzolo S, Shireman LM, Koehn J, McConnachie LA, Kraft JC, Shen DD, Ho RJY. “Three HIV Drugs, Atazanavir, Ritonavir, and Tenofovir, Coformulated in Drug-Combination Nanoparticles Exhibit Long-Acting and Lymphocyte-Targeting Properties in Nonhuman Primates.” J Pharm Sci. 2018 Dec;107(12):3153-3162. PMID: 30121315.

Koehn J, Iwamoto JF, Kraft JC, McConnachie LA, Collier AC, Ho RJY. “Extended cell and plasma drug levels after one dose of a three-in-one nanosuspension containing lopinavir, efavirenz, and tenofovir in nonhuman primates.” AIDS. 2018 Nov 13;32(17):2463-2467. PMID:30102655.

McConnachie LA, Kinman LM, Koehn J, Kraft JC, Lane S, Lee W, Collier AC, Ho RJY. “Long-Acting Profile of 4 Drugs in 1 Anti-HIV Nanosuspension in Nonhuman Primates for 5 Weeks After a Single Subcutaneous Injection.” J Pharm Sci. 2018 Jul;107(7):1787-1790. PMID: 29548975.

Kraft JC, McConnachie LA, Koehn J, Kinman L, Collins C, Shen DD, Collier AC, Ho RJY. “Long-acting combination anti-HIV drug suspension enhances and sustains higher drug levels in lymph node cells than in blood cells and plasma”. AIDS. 2017 Mar 27;31(6):765-770.

Kraft JC, Freeling JP, Wang Z, Ho RJY. “Emerging research and clinical development trends of liposome and lipid nanoparticle drug delivery systems.” J Pharm Sci 103:29-52. 2014.

Freeling JP, Koehn J, Shu J, Sun J, Ho RJY. “Long-Acting Three-Drug Combination Anti-HIV Nanoparticles Enhance Drug Exposure in Primate Plasma and Cells within Lymph Nodes and Blood.” AIDS 28: 2625-2631, 2015 (highlighted by an accompanying editorial commentary in AIDS).