Curtis Tyree is Senior Vice President, Strategy and Business Development, at Organovo. He is responsible for corporate partnerships, acquisitions, and R&D strategy. Prior to Organovo, Dr. Tyree held senior positions at HUYABIO, where he helped develop the immunomodulator HIYASTA™ through approval in Japan. At TorreyPines Therapeutics he presented on the first gamma secretase modulators for Alzheimer’s Disease, and at Ligand Pharmaceuticals helped discover the thrombopoietin mimic Promacta®. He holds a BSc in Microbiology & Immunology from McGill University and a PhD in Biology from UC San Diego. Dr. Tyree served as a founding member of the Advisory Board and as Adjunct Clinical Assistant Professor of Pharmacy Practice at the KGI School of Pharmacy and Health Sciences. He has served as an instructor and faculty member at the UC San Diego Division of Extended Studies.
Organovo Presentation at H.C. Wainwright Global Life Sciences Conference
Doug Cohen
Douglas Jay Cohen has served as president and Chief Executive Officer of IR Medtek LLC since January 2019, a medical device company developing a non-invasive probe for cancer detection by primary care physicians using a technology licensed from the Ohio State University. Prior to IR Medtek, Mr. Cohen served as President and Chief Executive Officer of Beacon Street Innovations, an advanced technology printing company from September 2016 to present. From January 1994 to September 2016, Mr. Cohen served as Vice President of Operations and Engineering at Screen Machine Industries, an industrial and construction heavy equipment manufacturer. As an active investor in startup companies, Mr. Cohen has invested in over 20 biotech startups in the past 10 years, including investing in Organovo in 2013 and maintaining a position in the company ever since. Mr. Cohen received a B.S. from the Massachusetts Institute of Technology.
David Gobel
David Gobel has served as Chief Executive Officer of Methuselah Fund LLC since December 2016 and as Chief Executive Officer of Methuselah Foundation since September 2001, promoting increasing the healthy human lifespan by various means including; performance prizes, targeted grant making, education, and the creation/funding of biotech startups. Mr. Gobel became Chief Venture Strategist at Transportation Security Administration from January 2009 until March 2013, where he was responsible for strategic planning, innovation management and creation of a novel Venture Capital capability for TSA and then Department of Homeland Security by partnering with In-Q-Tel. Mr. Gobel was a member of the board of Volumetric Biotechnologies, from April 2018 to January 2020, a company that focuses on the development of bioholographic human tissue printing. Since July 2018, Mr. Gobel served as member of the board for Turn Bio, and since May 2020 as chairman of the board of Turn Bio. Mr. Gobel has served as a board member of Leucadia Therapeutics since October 2015, and as an independent founding board member of Oisin Therapeutics since December 2014.
Alison Milhous
Alison Tjosvold Milhous has 20 years of audit and technical accounting experience and is a certified public accountant. She is currently the Vice President, Accounting at Erasca, Inc., a clinical-stage precision oncology company. Prior to joining Erasca, she was an independent consultant assisting public and private companies with accounting and reporting needs primarily within the life sciences and technology industries. Ms. Milhous was previously an audit partner at Grant Thornton LLP from August 2015 through September 2019 and held various positions with increasing responsibility at Grant Thornton from June 2002 as an audit associate through July 2015 as an audit senior manager. She began her career in June 2000 at Arthur Andersen LLP. Ms. Milhous served on the membership committee of Athena San Diego, a professional women’s leadership organization with a STEM focus, from August 2012 through September 2019 and was on the Pinnacle steering committee from September 2013 through April 2015. Ms. Milhous received a Bachelor of Science degree in Business Administration with a dual concentration in Accounting and Finance from California State Polytechnic University, San Luis Obispo.
Norman Staskey
Mr. Staskey is currently under agreement with Danforth Advisors, LLC and is a seasoned executive with significant experience in managing and leading teams as well as overseeing the financial and operational responsibilities of private and publicly traded life sciences companies. He has served as a Senior Director of Danforth since May 2021. Mr. Staskey has served as the Chief Financial Officer of Azitra, Inc. since October 2022. From September 2014 to May 2021, Mr. Staskey was employed by EY (formally Ernst & Young), most recently as a managing director in EY’s Financial Accounting and Advisory services practice. Mr. Staskey received his B.S. of Business Administration from Cleveland State University and is a Certified Public Accountant in the State of Ohio.
Keith Murphy
Keith Murphy is currently CEO and Chairman of Viscient Bio, Inc., and a serial entrepreneur and investor in biotech. Prior to co-founding Viscient Biosciences, Mr. Murphy founded Organovo Inc., in 2007 and led all company operations until 2017. He co-invented the NovoGen MMX bioprinter platform and grew Organovo through early investments and pharma corporate partnerships Prior to Organovo, Mr. Murphy spent ten years at Amgen in roles of increasing responsibility, including four years as the Global Operations Leader of denosumab, now marketed as Prolia & Xgeva ($4B+ annual sales). Prior to Amgen, he played a key role at Alkermes (NASDAQ:ALKS) in the successful development of once-monthly human growth hormone (hGH) in partnership with Genentech. He holds a B.S. in Chemical Engineering from the Massachusetts Institute of Technology and is an alumnus of the UCLA Anderson School of Management. Mr. Murphy serves as co-chair of the Board of No Patient Left Behind, and on the Board of Directors of the California Life Sciences Association, the state’s life science industry public policy, advocacy and business leadership organization.
Adam K. Stern
Adam K Stern is the CEO of SternAegis Ventures and has been the Head of Private Equity Banking at Aegis Capital Corp since 2012. Prior to SternAegis, from 1997 to 2012, he was Senior Managing Director at Spencer Trask Ventures, Inc., where he managed the structured finance group focusing primarily on technology and life science companies. From 1989 to 1997, Mr Stern was at Josephthal & Co., Inc., Members of the New York Stock Exchange, where he served as Head of Private Equity and Managing Director. He has been a FINRA licensed securities broker since 1987 and a Registered General Securities Principal since 1991. Mr. Stern has been a founding investor in numerous private and public companies and currently serves as a Director of DarioHealth Corp. (Nasdaq: DRIO), Matinas BioPharma Holdings, Inc. (NYSE: MTNB), Aerami Therapeutics, Inc. and HydroFarm Holdings, Inc. Mr. Stern graduated from the Lear School, Miami Florida in 1982 and The University of South Florida in 1987.
Bioprinted pluripotent stem cell-derived kidney organoids provide opportunities for high content screening
Recent advances in the directed differentiation of human pluripotent stem cells to kidney organoids advances the prospect of drug screening, disease modelling, and even restoration of renal function using patient-derived stem cell lines. Here, we demonstrate the successful adaptation of our directed differentiation protocol to the NovoGen Bioprinter® MMX technology to achieve automated, rapid fabrication of self-organizing kidney organoids. Bioprinted organoids were found to be equivalent to those previously reported via manual generation at both the level of morphology and component cell types, as well as gene expression patterns and cell clusters revealed by single cell transcriptional profiling. Utilization of a bioprinter allows for the generation of large numbers of uniform and highly reproducible organoids in reduced time (approximately 20x faster) compared to manual processes. Treatment of bioprinted kidney organoids cultured in conventional 6-well format with doxorubicin exhibited concentration-dependent morphological changes consistent with cell injury and degeneration. Consistent with clinical observations, doxorubicin showed distinct glomerular toxicity with marked increases in cleaved caspase 3 mRNA and protein, accompanied by loss of podocyte-specific cell markers. Proof of concept high-throughput toxicity screening was achieved with bioprinted kidney organoids in 96-well Corning® Transwell® plates treated for 72 hours with a range of doxorubicin concentrations (0.2 to 25 µM). Analysis of 6-well and 96-well cell viability data suggested that organoids printed in both multi-well plate formats were similarly sensitive to doxorubicin. The doxorubicin IC50 for organoids bioprinted in 6-well plates was 3.9 ± 1.8 µM (value ± S.E.), while the calculated IC50 for organoids bioprinted in a 96-well plate was 3.1 ± 1.0 µM. Collectively, these results suggest that bioprinted kidney organoids are functionally equivalent to those prepared manually and thus are likely to be useful for toxicity screening, the development of iPSC-based approaches for the interrogation of complex disease phenotypes, and the scaling needed for clinical restoration of renal function with patient-derived iPSCs.
Cells isolated from donors with nonalcoholic fatty liver disease exhibit disease phenotypes in 3D bioprinted human liver tissue
The identification of targets and biomarkers and development of therapeutics for nonalcoholic fatty liver disease (NAFLD) may be accelerated by the use of well-characterized primary cell and tissue reagents, as well as improved in vitro human cell-based disease models, including three-dimensional (3D) bioprinted liver tissue. The characteristics of donors from which the cells are isolated, and especially their stage on the NAFLD continuum, are likely to influence the resulting performance in two-dimensional (2D) and 3D models. Evaluation of individual cell type characteristics, and their performance when combined in a tissue coculture model, could enable development of in vitro models more representative of specific patient populations and disease phenotypes.
RNA sequencing (RNA-seq) was performed on (5) non-diseased and (5) NAFLD liver tissues with NAFLD Activity Score (NAS) of 3 or more, revealing clear separation of non-diseased vs. NAFLD tissues and differential expression of fibrosis related genes. Histological analyses performed on tissue microarrays revealed consistent altered distribution patterns of hepatic stellate cells (HSC), with differential activation of HSC. Hepatocytes and non-parenchymal cells (NPC) (HSC, endothelial cells, and Kupffer cells), were isolated from non-diseased donors and from donors with NAS of 3 or more. The isolated cells were characterized with respect to viability, growth kinetics, cytokine production, and phenotype. 3D bioprinted liver tissue was generated using either NPCs isolated from diseased donors combined with non-diseased hepatocytes, or hepatocytes isolated from diseased donors combined with non-diseased NPCs. 3D bioprinted liver tissue generated using NPCs from a diseased donor exhibited accelerated collagen deposition (by trichrome stain) and HSC activation (by α-SMA staining) in comparison to bioprinted liver tissue generated with non-diseased tissue donors. Tissue generated using hepatocytes from a diseased donor exhibited steatosis induction.
Characteristics of the tissue of origin for cells used for in vitro models, including disease status, influence the performance of the cells and the utility of the resulting model. Thus, characterization of cell donors could enable development of in vitro models more representative of specific patient populations and disease phenotypes.
