March 2014 | VOL. 13, NO. 3 | McGowan Institute  Newsletter

McGowan Institute Holds Its Annual Scientific Retreat
 
 
 

The McGowan Institute for Regenerative Medicine held its 2014 Scientific Retreat March 9-11, 2014. The focus was on peer-to-peer networking, and the retreat provided many opportunities to explore collaborative endeavors with other researchers, participating guests, and external partners who are working to bring regenerative medicine technologies to clinical use.

The participation and contributions of the guests and external collaborators - along with McGowan Institute for Regenerative Medicine affiliated faculty and trainees - provided for insightful discussions and identification of opportunities for partnership. This year's program was chaired by Kacey Marra, PhD, Associate Professor in the Departments of Plastic Surgery (primary) and Bioengineering (secondary), as well as Co-Director of the Adipose Stem Cell Center at the University of Pittsburgh.

 

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RESOURCES AT THE MCGOWAN INSTITUTE


UPCOMING EVENTS


SCIENTIFIC ADVANCES

  • Study Finds Mechanism for Increased Activity of Oncogene in Head and Neck Cancers
  • Lizards May Answer Cartilage Regeneration Mystery
  • Biomarkers That Can Provide Advance Warning of Deadly Kidney Condition in Critically Ill Patients Identified
  • Pitt Researchers to Study New Treatments for Pancreatic Cancer Patients
  • Innovative Brain Imaging Technology Receives DSF Charitable Foundation Funding
  • Pitt Establishes Brain Institute to Unlock Mysteries of the Brain, Discover Novel Therapies

  • AWARDS AND RECOGNITION


    OTHER


    Publication of the Month | March 2014

    Authors: Lui VW, Peyser ND, Ng PK, Hritz J, Zeng Y, Lu Y, Li H, Wang L, Gilbert BR, General IJ, Bahar I, Ju Z, Wang Z, Pendleton KP, Xiao X, Du Y, Vries JK, Hammerman PS, Garraway LA, Mills GB, Johnson DE, Grandis JR.

    Title: Frequent mutation of receptor protein tyrosine phosphatases provides a mechanism for STAT3 hyperactivation in head and neck cancer.

    Summary: The underpinnings of STAT3 hyperphosphorylation resulting in enhanced signaling and cancer progression are incompletely understood. Loss-of-function mutations of enzymes that dephosphorylate STAT3, such as receptor protein tyrosine phosphatases, which are encoded by the PTPR gene family, represent a plausible mechanism of STAT3 hyperactivation. We analyzed whole exome sequencing (n = 374) and reverse-phase protein array data (n = 212) from head and neck squamous cell carcinomas (HNSCCs). PTPR mutations are most common and are associated with significantly increased phospho-STAT3 expression in HNSCC tumors. Expression of receptor-like protein tyrosine phosphatase T (PTPRT) mutant proteins induces STAT3 phosphorylation and cell survival, consistent with a "driver" phenotype. Computational modeling reveals functional consequences of PTPRT mutations on phospho-tyrosine-substrate interactions. A high mutation rate (30%) of PTPRs was found in HNSCC and 14 other solid tumors, suggesting that PTPR alterations, in particular PTPRT mutations, may define a subset of patients where STAT3 pathway inhibitors hold particular promise as effective therapeutic agents.

    Source: Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):1114-9. doi: 10.1073/pnas.1319551111. Epub 2014 Jan 6.


    Grant of the Month | March 2014

    PI: Peter Wearden

    Co Investigator: Trevor Arnoult Snyder

    Title: Small blood pumps for small patients

    Project Description: Heart failure and congenital heart defects threaten the lives of several thousand children each year. The only FDA-approved long term pediatric heart support device is the Berlin Heart Excor, which is based on 30+ year old technology and is fraught with complications including blood clots forming in the device requiring frequent device replacement. The recipients of this technology are at high risk for strokes, bleeding, and infection and the pumps are driven by a large 220 lb console, which limits patient mobility and prevents hospital discharge. In spite of these severe limitations, 90% of Excor recipients survive to transplant, although the median duration of support is only 35 days. A safer device would dramatically reduce the complications of support, permit discharge to home, and allow doctors to deploy the technology earlier, before a child reaches the brink of death. VADovations is developing a miniature implantable pump platform, the Revolution, in which minor modifications of 2 components can be implemented to adjust the pump performance to support the right or left side of the heart. The devices are 8 mm in diameter and 50 mm in length, about the size of a 'AAA'battery, compared to the market leading Heartmate II, which is 47 mm in maximum diameter and 95 mm in length, the size of a 'D'cell battery. Our adult Revolution RVAD can safely generate the lower blood rates needed for a pediatric left heart assist device and has demonstrated exceptionally low blood trauma in bench-top studies and during implants in sheep for durations up to one month with no long-term blood thinners. Building upon these promising results, we propose a Fast Track, combined Phase I/II SBIR to re-purpose the Revolution RVAD as a pediatric left heart assist device, the Revolution MINI, for children ages 1 and up. Then we will revise the design to create the Revolution NEO for neonates and infants, aged 0-1, who represent the largest clinical need for pediatric heart support. During Phase I, we will demonstrate the feasibility and efficacy of the MINI for pediatric blood flow rates and pressures during in vitro and short term animal experiments. In Phase II, we will conduct chronic animal implants to evaluate the long-term function, biocompatibility, and durability of the pumps and perform verification and validation studies of the Revolution MINI system to prepare for a US clinical trial. Throughout the program, we will focus considerable efforts on anatomic fit modeling and studies to devise approaches so that these devices can be implanted in the smaller bodies of children, to avoid pumps protruding from the body, as occurs with the paracorporeal Excor. Superior hemocompatibility, smaller size, and the ability to leverage adult system components, combine to produce pediatric heart assist devices that will offer fewer complications, permit patient discharge to home, and be economically viable to revolutionize the treatment of pediatric heart failure.

    Source: National Heart, Lung, and Blood Institute

    Term: 02/15/2014 – 07/31/2014

    Amount:  $400,545


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