The Institute for Advancing Medical Innovation: stepping into the future of drug discovery, delivery and biomedical engineering

System requirements: Windows Media Player version 9 or above.Inspired by the opportunity to grow educational and entrepreneurial capacity, the Institute for Advancing Medical Innovation (IAMI) was established upon the belief that: ideas are translated to innovation to improve health. The Institute will focus on education and research that advances medical innovations. The result will ultimately accelerate the number and quality of new drugs, medical devices and drug-medical device combinations flowing from the investigators bench to the patient's bedside. Guided by an advisory board of independent experts and staffed by experienced drug development and medical device leaders, the Institute is designed to create an unprecedented collaboration of resources and processes to support the following key objectives: Advance new, novel medical innovations for the diagnosis, treatment, prevention and control of human and animal disease; Create a culture of multi-disciplinary, multi-organizational collaboration focused on advancing medical innovations from discovery to commercialization; Conduct clinical proof of concept trials on new, novel medical innovations; and prepare graduate and postdoctoral students for careers in development and commercialization of medical innovations. The Institute was created with a gift of $8.1 million from the Kauffman Foundation with a challenge match of$8 million from KU Endowment

Open Access High Throughput Drug Discovery in the Public Domain: A Mount Everest in the Making

High throughput screening (HTS) facilitates screening large numbers of compounds against a biochemical target of interest using validated biological or biophysical assays. In recent years, a significant number of drugs in clinical trails originated from HTS campaigns, validating HTS as a bona fide mechanism for hit finding. In the current drug discovery landscape, the pharmaceutical industry is embracing open innovation strategies with academia to maximize their research capabilities and to feed their drug discovery pipeline. The goals of academic research have therefore expanded from target identification and validation to probe discovery, chemical genomics, and compound library screening. This trend is reflected in the emergence of HTS centers in the public domain over the past decade, ranging in size from modestly equipped academic screening centers to well endowed Molecular Libraries Probe Centers Network (MLPCN) centers funded by the NIH Roadmap initiative. These centers facilitate a comprehensive approach to probe discovery in academia and utilize both classical and cutting-edge assay technologies for executing primary and secondary screening campaigns. The various facets of academic HTS centers as well as their implications on technology transfer and drug discovery are discussed, and a roadmap for successful drug discovery in the public domain is presented. New lead discovery against therapeutic targets, especially those involving the rare and neglected diseases, is indeed a Mount Everestonian size task, and requires diligent implementation of pharmaceutical industry’s best practices for a successful outcome

Three-Dimensional Cell Culture Assays: Are They More Predictive of In Vivo Efficacy than 2D Monolayer Cell-Based Assays?

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140110/1/adt.2015.29001.rtd.pd

The Third International Meeting on Genetic Disorders in the RAS/MAPK Pathway: Toward a Therapeutic Approach

The Third International Meeting on Genetic Disorders in the RAS/MAPK Pathway: Towards a Therapeutic Approach was held at the Renaissance Orlando at SeaWorld Hotel (August 2-4, 2013). Seventy-one physicians and scientists attended the meeting, and parallel meetings were held by patient advocacy groups (CFC International, Costello Syndrome Family Network, NF Network and Noonan Syndrome Foundation). Parent and patient advocates opened the meeting with a panel discussion to set the stage regarding their hopes and expectations for therapeutic advances. In keeping with the theme on therapeutic development, the sessions followed a progression from description of the phenotype and definition of therapeutic endpoints, to definition of genomic changes, to identification of therapeutic targets in the RAS/MAPK pathway, to preclinical drug development and testing, to clinical trials. These proceedings will review the major points of discussion

Overcoming Wnt–β-catenin dependent anticancer therapy resistance in leukaemia stem cells

Leukaemia stem cells (LSCs) underlie cancer therapy resistance but targeting these cells remains difficult. The Wnt–β-catenin and PI3K–Akt pathways cooperate to promote tumorigenesis and resistance to therapy. In a mouse model in which both pathways are activated in stem and progenitor cells, LSCs expanded under chemotherapy-induced stress. Since Akt can activate β-catenin, inhibiting this interaction might target therapy-resistant LSCs. High-throughput screening identified doxorubicin (DXR) as an inhibitor of the Akt–β-catenin interaction at low doses. Here we repurposed DXR as a targeted inhibitor rather than a broadly cytotoxic chemotherapy. Targeted DXR reduced Akt-activated β-catenin levels in chemoresistant LSCs and reduced LSC tumorigenic activity. Mechanistically, β-catenin binds multiple immune-checkpoint gene loci, and targeted DXR treatment inhibited expression of multiple immune checkpoints specifically in LSCs, including PD-L1, TIM3 and CD24. Overall, LSCs exhibit distinct properties of immune resistance that are reduced by inhibiting Akt-activated β-catenin. These findings suggest a strategy for overcoming cancer therapy resistance and immune escape

Twenty-First Century Diseases: Commonly Rare and Rarely Common?

Alzheimer's drugs are failing at a rate of 99.6%, and success rate for drugs designed to help patients with this form of dementia is 47 times less than for drugs designed to help patients with cancers ( www.scientificamerican.com/article/why-alzheimer-s-drugs-keep-failing/2014 ). How can it be so difficult to produce a valuable drug for Alzheimer's disease? Each human has a unique genetic and epigenetic makeup, thus endowing individuals with a highly unique complement of genes, polymorphisms, mutations, RNAs, proteins, lipids, and complex sugars, resulting in distinct genome, proteome, metabolome, and also microbiome identity. This editorial is taking into account the uniqueness of each individual and surrounding environment, and stresses the point that a more accurate definition of a “common” disorder could be simply the amalgamation of a myriad of “rare” diseases. These rare diseases are being grouped together because they share a rather constant complement of common features and, indeed, generally respond to empirically developed treatments, leading to a positive outcome consistently. We make the case that it is highly unlikely that such treatments, despite their statistical success measured with large cohorts using standardized clinical research, will be effective on all patients until we increase the depth and fidelity of our understanding of the individual “ rare ” diseases that are grouped together in the “ buckets ” of common illnesses. Antioxid. Redox Signal. 27, 511–516

Impact of high-throughput screening in biomedical research

High Throughput Screening (HTS) has been postulated in several quarters to be a contributory factor to the widespread decline in Pharma industry productivity. Moreover, it has been promoted as anti-scientific and labeled as responsible for stifling the creativity that has long been the lifeblood of drug discovery. In this article we aim to dispel some of these myths and present the case for the use of HTS as part of a proven scientific toolkit, the wider use of which is essential for the discovery of new chemotypes. As we gain an even deeper understanding of the underlying mechanistic causes of disease, HTS has been further embraced in academic quarters for the discovery of tool compounds. Its wide adoption in industry and academia is a clear indicator that this technique is a valuable asset for the discovery of novel bioactive substances that can be used as molecular probes or optimized to pharmaceutical products