Past Awardees

BRIght Futures Prize

2017 

 

Ellen Bubrick, MD

Project Title: Low Intensity Focused Ultrasound for Drug Resistant Epilepsy

Abstract: Focused Ultrasound Treatment for Refractory Epilepsy: An Efficacy Trial Epilepsy is one of the most common neurologic disorders, affecting 2.5 million Americans and 65 million people worldwide. Approximately 70% of patients with epilepsy achieve seizure control with medications, leaving 30% of patients with persisting seizures despite medication. Ongoing seizures can be very debilitating, and are often associated with significant morbidity and even mortality. There are very few new treatments, pharmacologic or non-pharmacologic, coming down the pipeline to address this often desperate, at-risk population. Despite this, the importance of reducing patients’ seizure burden remains high. Aside from epilepsy surgery, for which only a percentage of these patients are eligible, there are few other options to help reduce seizure frequency in this population. Neurostimulatory devices such as Responsive Neurostimulation (Neuropace) and Vagal Nerve Stimulation (VNS) have been shown to be of some benefit, though these are limited to small, specific patient populations and responses vary. Newer devices have been modeled on the success seen in movement disorders, such as Parkinson’s disease. One very successful approach for treatment of tremor is focused ultrasound. At higher intensities, focused ultrasound can ablate tissue, therefore it is also used to treat brain tumors. There is some evidence that low intensity focused ultrasound may be helpful in treating seizures. It has been shown to be safe in humans, and has proven neuromodulatory effects on human brain function as well. This idea of neuromodulation, or mechanical disruption of neural networks to treat disease, is accelerating quickly and data on such efforts are accumulating data rapidly. We propose a prospective interventional clinical trial using low intensity focused ultrasound to treat drug-resistant temporal lobe epilepsy.

 

 

 

2016

 

David Levine, MA, MD

Project Title: Hospitalization at Home: The Acute Care Home Hospital Program for Older Adults

Abstract: Hospitals are the standard of care for acute illness, but hospital care is often unsafe, inaccessible, and expensive for older individuals. While admitted, 20% suffer delirium, over 5% contract hospital-acquired infections, and most lose functional status that is never regained. Timely access to hospital care is poor: many wards are overcapacity, and emergency department waits are protracted. Moreover, hospital care is increasingly costly. We propose a home hospital model of care that substitutes for treatment in an acute care hospital. Studies of the home hospital model have demonstrated that acute care can be delivered in the home with equal quality and safety, reduced cost, and improved patient experience. While this is the standard of care in several developed countries, only 2 small US-based non-randomized pilots have materialized. Our pilot innovates on prior home hospital models by translating biomedical device science into clinical workflows employing a randomized controlled assessment, virtual clinician visits, remote/wireless vital sign monitoring, patient physical activity and sleep monitoring, machine-learning predictive analytics, point-of-care bloodwork, and community health workers. Successful demonstration of the home hospital model will enable hospitals, accountable care organizations, and care networks to launch an evidence-based cost-effective medical service in the homes of acutely ill older adults.

 

 

 

2015

 

Wilfred Ngwa, PhD

Project Title: Biomaterial drones: 4G technology to enhance treatment of cancer metastasis with minimal collateral damage

Abstract: Metastasis accounts for over 90% of all cancer associated suffering and death and arguably presents the most formidable challenges in cancer management. The central innovation and overall goal of this project is the development of fourth generation (4G) radiotherapy biomaterials to significantly enhance the treatment of metastasis at no additional inconvenience to cancer patients. The new 4G biomaterials are designed to simply replace the inert biomaterials (fiducials/spacers), which are currently routinely implanted to ensure spatial accuracy during radiotherapy. The new biomaterials specifically incorporate a payload of nontoxic targeted radiosensitizing gold nanoparticles (GNP), and immunoadjuvants in a biodegradable polymer matrix. Once in place, the 4G biomaterials controllably release the payload directly into the tumor as the polymer degrades. During radiotherapy, the released GNP will significantly enhance local tumor cell kill, and work with the released immunoadjuvant to prime a robust T cell response. A robust T cell response can kill metastatic cells distant from the irradiated site (abscopal effect), with major potential to help prevent cancer recurrence. Slow in-situ release of the payload will minimize systemic/overlapping toxicities, which are currently a critical barrier/concern with competing approaches. Overall, our technology could significantly enhance survival and quality of life for lung/pancreatic/prostate cancer patients.

 

 

 

 

2014

 

Hadi Shafiee, PhD

Project Title: A low-cost hand-held microchip device for rapid HIV detection and treatment monitoring through viral load measurement on paper with flexible electronics

Abstract: To increase access to HIV care and antiretroviral therapy (ART) worldwide and to improve treatment outcomes, there is an urgent need for significantly reducing the cost per HIV diagnostic test by developing innovative and inexpensive diagnostic tools. Despite the urgent need for viral load monitoring, there is currently no commercially available and inexpensive POC viral load assay. Here, building upon our prior expertise, we will use nano- and micro-scale approaches to develop a microfluidic device that achieves label-free viral load measurement. We will validate this device with HIV-infected patient samples. The underlying hypothesis of this proposal is that viruses can be selectively captured on the surface of microfluidic devices using anti-gp120/gp41 antibodies and detected using electrical sensing of the viral lysate. The proposed platform technology relies on three technological advances: (i) capture of multiple HIV-1 subtypes with high efficiency, specificity, and sensitivity on microchips, (ii) label-free electrical detection using a portable system, and (iii) paper-based microfluidic fabrication as an inexpensive, disposable, and mass producible method appropriate for POC diagnosis. In addition, such a platform technology has potential broad applications for other diseases such as influenza, herpes, hepatitis, malaria, and tuberculosis.

 

 

 

2013

 

Utkan Demirci, PhD

Project Title: Disposable Chips to Detect Antiepileptic Drug Serum Concentrations at the Point of Care using Nanoplasmonic Platform

Abstract: Optimizing the effectiveness of antiepileptic drugs (AEDs) involves adjusting dosages and the timing of dosages to minimize side effects and maximize seizure control. Utilizing AED serum concentrations can guide this process, but obtaining blood tests is presently impractical due to the associated inconvenience (lab based detection) and costs, as well as the often long latency between side-effects and/or seizures and when blood tests are obtained. Here, we propose to develop a microfluidic based disposable AED detection that can be performed anywhere and automated to handle 10-100 μL of blood obtained with a finger-prick, such as used for blood glucose monitoring. The glass surface coated with gold nanoparticles is functionalized with anti-AED antibody for specific capture of AED molecules. Upon drug-Ab binding, a shift in the extinction intensity and wavelength spectrum would be seen due to localized surface plasmon resonance effect of gold nanoparticles. The proposed system consists of a portable spectrophotometer for detection and gives results in approximately 10 minutes. A version of this device could be made with read-outs that the patient or family member can monitor, to report to the physician or to implement actions that the physician provided them in advance.

 

 

 

2012

 

Robert Green, MD, MPH

Project Title: BabySeq: A Pilot Project to Explore Genomic Screening of Newborns

Abstract: Genomic medicine has arrived and is rapidly being integrated into the practice of medicine. A multi-disciplinary team at Brigham and Women’s Hospital (BWH), supported through the NIH-funded MedSeq Project, is already on the leading edge of designing interpretational pipelines and physician reports in order to deliver the results of whole genome sequencing (WGS) in 200 adults, and has designed extensive qualitative and quantitative outcome studies to understand the downstream behavioral and medical consequences of implementing genomic medicine in this population. The next uncharted and highly controversial arena is whether WGS should be used to screen newborns in order to detect risks for future diseases. In this BRIght Futures application, we propose to use a randomized factorial design to gather critical preliminary data on the preferences of parents towards genomic screening of their newborns, and to conduct pilot sequencing and reporting of WGS results to the parents of 10 healthy newborns.

 

Director's Transformative Awards

2017

 

Terrie Inder, MD, MBChB

Project Title: Healthy Starts to Life: Transformative Award in Newborn Research

Abstract: The health of the pregnant woman, fetus, and newborn infant forms the foundation for health throughout the life course. As conceptualized by the Developmental Origins of Health and Disease paradigm, adverse experiences early in development have a profound impact on one’s risk for chronic diseases later in life, including asthma, hypertension, diabetes, neuropsychiatric and neurodegenerative disorders. With this BRI Transformative Award, we propose to build a new neonatal and childhood research platform, that will both expand on the existing LIFECODES platform alongside more in depth pipelines for targeted populations of high-risk infants. LIFECODES is one of the nation’s largest pregnancy (n>4,000) cohort studies with an extensive biobank of samples (blood, urine, and placenta) collected during pregnancy to research biomarkers of pregnancy complications including preterm birth and preeclampsia. To date, limited neonatal and no childhood data has been collected for these pregnancies. In part one of the platform, we will engage prospectively enrolling LIFECODES mothers to facilitate collection of more extensive neonatal data and specimens with opportunity for later childhood outcomes. This research platform will be established in collaboration with LIFECODES investigators (Maternal-Fetal Medicine), Precision Medicine (Pathology), Bioinformatics (HMS and Partners). In part two of the platform, we will develop a more in-depth investigational pipeline for pilot data characterization of several high-risk populations of infants (approx. 20-30 mother-infant pairs per group) that are the focus of multiple investigators within BWH. The first patient group will be a control group of uncomplicated term pregnancies and healthy infants. For the at-risk infant groups, we will focus on a) infants born very preterm (<32 weeks’ gestation); b) term born infants exposed in-utero to maternal selective serotonin reuptake inhibitors; c) infants with hypoxic-ischemic brain injury; and finally, d) infants with Down Syndrome.

 

 

 

 

Michael Brenner, MD

Disease Deconstruction by Single Cell Transcriptomics: Onsite Single Cell RNA-seq Core

Abstract: A next step in understanding tissue pathology across diseases is the identification of abnormal infiltrating cells and pathologic changes in the tissue parenchymal cells and stroma at the single cell level. Molecular studies on whole tissues and enriched cell types provide a global picture of pathological processes, while single cell analyses provide a new look at the nature of cell types, cell states, cellular interactions, and molecular pathways that may be obscured in bulk populations. Inflammation is one type of pathologic process that underlies a broad range of medical conditions. The BWH Human Immunology Center and the Evergrande Center for Immunologic Diseases both emphasize inflammation and the power single cell and high- dimensional analyses, including flow cytometry, mass cytometry (CyTOF) and RNA sequencing (RNA-seq), to reveal critical cell types and pathways active in blood, fluids and end organs in many diseases. The advent of droplet-based single cell transcriptomics analyses, led by the 10X Genomics platform, now offers the ability to assess single cells from patient samples (or animal models) in dramatic transcriptomic detail and has the potential to identify new pathologic cell subsets and phenotypes that may be targeted therapeutically. When abnormal tissues are disaggregated and analyzed by single cell transcriptomics, an integrated picture of the inflammatory pathways present and changes in the transcriptomes of the tissue parenchymal cells and stroma provide an unprecedented detailed and composite picture of organ pathology and inflammation. Here, we propose to implement the 10X genomics technology at BWH, with an integrated platform that includes technical expertise in processing and analyzing samples, bioinformatics support for data analysis, and pilot funding to help facilitate adoption by investigators new to the technology. We expect that this platform will empower single-cell transcriptomic studies across hospital departments, disease centers, laboratories and clinical divisions. Single cell disease deconstruction studies have the potential to reveal new pathologic cell states in both the immune compartment and in organ tissue cells. Defining pathologic processes at the state of the art level is now possible with single cell transcriptomics and is highly sought by academic investigators and the pharmaceutical industry.

 

 

 

2016

 

Oliver Jonas, PhD

Project Title: Lab-in-a-patient Microdevices for Next-Generation Precision Medicine

Abstract: Despite technological advances in experimental biology and genomics, our understanding of disease pathophysiology and therapeutic decision-making often rely upon inferences based on incomplete snapshots of data rather than the intricate variations across space, time, and cellular components that characterize living tissues. In lung cancer, for instance, there is currently no functional characterization of suspected lesions to aid clinical decision-making among various surgical or systemic treatment options. This project will develop novel micro-scale “labinapatient” technology that allows for the first time in a single system – monitoring and probing the disease microenvironment in real-time within human tissue. Using implantable microdevices that are inserted directly into tissue, we provide phenotypic readouts for 120 distinct therapies or molecular sensors from a single tumor in real-time using integrated optical microsensors, in a minimally invasive manner and without systemic toxicities. Such comprehensive functional profiling of the tumor may be integrated with existing interventional and surgical procedures, and enable superior therapeutic decision-making in lung cancer and beyond. Support from the BRI for this project will unite efforts in the Biomedical Imaging Program, Cancer Research Center and Center for Surgical Innovation to advance the technology into neartermuse in first-in-man clinical studies to be conducted at BWH.

 

 

 

2015

 

Bohdan Pomahac, MD and Elazer Edelman, MD, PhD

Project Title: Controlled Artificial Perfusion of Tissues using Organ Function Markers

Introduction: Our Partners-based center will support: (i) resuscitation of organs in failure, and (ii) preservation of organs procured for allotransplantation. Current [1] organ support devices provide flow with minimal regard to the need of the native tissues [2] – we will change that by embedding sensors for metrics of tissue function that will drive the support provided by the device in an individualized manner. At the same time, we will change how we procure organs for transplantation, by replacing the ice baths used to transport these precious tissues with controllable perfusion pumps. In both cases, organ support will depend on organ function. We will assay and display organ state, therefore channeling support towards the restoration of viability ex vivo and in vivo. A Partners-based center that enables patient- and organ-specific artificial perfusion will bring together scientists, clinicians, and engineers in a way not previously considered, and will further coalesce interested partners from many domains by operating in a modular manner. The commonality of needs between support of organs in failure and preservation of procured organs will further enable efficient use of resources and leveraging of learning. The BWH Perfusion Center will thus provide modular support for clinician-investigators who want to support patients in organ failure, study organ perfusion in failure and health, and make our institution singular in the instigation and care of these critical diseases. The impact on BWH, Partners and global medicine will be profound. We will establish a world-class center that draws on unique clinical insight, active cutting edge scientific research and innovative engineering science to extend support to organs in failure and enhance viability of organs for transplantation. The need is acute. Mechanical support of heart, liver, kidney and limb is emerging as a viable option [1, 3, 4], but the resources needed to support such a clinical program are prohibitive and as a result few patients receive these devices, and at massive costs.[2, 5] This year in the United States, 12,340 life-saving transplants have been performed, but 122,410 patients are still waiting to receive their transplants [6] because of shortage in organ availability or because procured organs cannot be kept viable long enough to travel to a recipient. Our Center will enable clinicians and investigators to come together to create a place to develop organ and patient-specific support and at the same time increase organ

 

 

 

 

Guillermo Garcia-Cardena, PhD

Project Title: Program in Human Rare (Orphan) Disease Modeling and Therapeutics

 

 

 

 

 

Richard Maas, MD, PhD

Project Title: Brigham Genomic Medicine (BGM): An Integrated BWH-wide Genomics Pipeline for Disease Gene Discovery

Abstract: The application of genomic sequencing to clinical medicine will transform disease diagnosis and treatment. As part of a programmatic effort to build genomic medicine at BWH, we are now using genome sequence to solve undiagnosed cases. This includes an integrated genomic medicine service, Brigham Genomic Medicine, or BGM, focused on monogenic case referrals from multiple BWH departments, a state-of-the-art computational pipeline, and an integrated interdisciplinary team for causal variant identification and disease gene discovery. BWH patients with monogenic diseases of unknown cause are not uncommon. Discovering the genetic causes of these disorders can help patients, advance BWH’s standing in genomic medicine, and facilitate discovery of therapeutic targets for these conditions and for more common disorders with similar phenotypes. We propose two Aims to accomplish these goals. In Aim 1, we will extend the referral base throughout BWH and employ our WES/WGS analysis pipeline to identify new disease causing variants and genes. In Aim 2, we will optimize our functional assessment platform and establish the burden of these monogenic variants in phenotypically related common diseases using genomic sequence repositories and the Partners Biobank. These efforts will transform patientcentered gene discovery, uncover therapeutic targets, and provide commercially valuable knowledge about disease pathways.

 

Health & Technology Innovation Awards

2017

 

Sean Lawler, PhD

Development of brainpenetrating and tumorspecific fluorinated peptides as glioblastoma therapeutics

 

 

 

 

 

Christopher French, MD

Targeting NUT in NUT midline carcinoma

 

 

 

 

 

Christopher Williams, PhD

A Virtual Reality Platform for Medical Image Visualization, Manipulation, and Radiation Therapy Planning

 

 

 

 

 

Reza Abdi, MD

Microengineering third party off shelf biological skin construct for burn patient

 

 

 

 

 

2016

 

Sophia Koo, MD

A Rapid Breath Test for Community Acquired Pneumonia

 

 

 

 

 

William Savage, MD, PhD

A pediatric-specific apheresis device using acoustic separation of blood

 

 

 

 

 

2015

 

Louis Nguyen, MD, MBA, MPH

A pilot study to measure peripheral blood flow in the lower extremities using an Enhanced Video Procedure

 

 

 

 

 

Jeffrey Karp, PhD

Safe battery to mitigate injuries from accidental ingestion

 

 

 

 

 

Richard Sherwood, PhD

Simplified high-throughput reprogramming screening

 

 

 

 

 

2014

 

Jeffrey Karp, PhD

A New Axis for Resolving Dysbiosis

 

 

 

 

 

Tracy Young-Pearse, PhD

Deciphering the Nature of Selective Neuronal Vulnerability in Alzheimer’s Disease

 

 

 

 

 

Aditi Hazra, MPH, PhD

IN SItu Genomics, Healthcare, and Treatment (INSIGHT) Study

 

 

 

 

 

Benjamin Humphreys, MD, PhD

A Primary Myofibroblast Progenitor Screen to Discover Antifibrotic Therapies

 

 

Research Excellence Awards

2016
Nicola Alesi, Muhammad Ali Chaudhary, Tara Deelman, Navin Gupta, Mohammad Islam, Kimberly Johnson, Stephania Libreros Ruiz, Carmela Passaro

 

2015
Ana Paula Abreu, MD, PhD; Benjamin Freedman, PhS; Taotao Lao, PhD; Wei Li; Sahar Nissim, Md, PhD; Joana Pereira das Neves, PhD; Chuan Wu

 

2014
Jessica Allegretti , MD; Prajna Behera, MS; Choi-Fong  Cho, PhD; Devaveena Dey, PhD; Brian Fissel; Amanda  Foks, PhD; Krista Hachey, MD; Annie Lewis-O’Connor, NP, PhD, MPH; Cecilia Martin, PhD; Zehra Ordulu ,MD; Arun Rooj, PhD; Jeremy Winkler, PhD; Lai-Ming Yung, PhD

 

2013
Ana Paula Abreu,  MD, PhD; Anne-Karin Arndt, MD; Julia Charles, MD, PhD; Benjamin Freedman, PhD;  Jeffrey Frost, BA;, Taotao Lao, PhD; Wei Li, Sahar Nissim, MD, PhD; Joana Pereira das Neves, PhD; Xinghui Sun, PhD; Lai-Ming Yung, PhD

 

2012
Kimberly Bertrand, ScD, MPH; Richard Burwick, MD, MPH; Katherine Gregory, PhD, RN; Basak Icli PhD; Christine Guo Lian, MD; Junjie Lu, PhD; Steven Jay, PhD; Shuchi; Mittal, PhD; Marta McCrum, MD; Zehra Ordulu, MD; Hiro Tatesu, PhD, MD; Xuehong Zhang, MD, ScD; Xiaobo Zhou, PhD

 

2011
Brandon Abbs, Damir Khabibullin, Binh Nguyen MD, Lei Qin, Xinghui Sun, Yuexiang Wang, Yufei Xu

 

2009
Karla Evans, PhD; Chiara Grisanzio, MD; Salil Anil Lachke, PhD; Margaret McLaughlin-Drubin, PhD and Iman Schultz, PhD.

 

2008
Benjamin E. Gewurz; Bradley A. Maron; Cysteinyl Thiol; Gabriela Orasanu; Alireza Radmanesh; Irfan Saadi; Astrid Suchy-Dicey; Polakit Teekakirikul; Hiroko Yano; Belinda Yap

 

2007
Amy Baldwin, PhD; Suzy D.C. Bianco, PhD; Zhuoxiao Cao, MD, PhD; Joshua J. Gooley, PhD; Jiali Han, PhD; Kerry Kocher; Juliet Moncaster, PhD; Sorachai  Srisuma, MD, PhD; Joseph Walpole; James Wells, PhD; Tracy Young-Pearse, PhD; Yi Yu, PhD

Stepping Strong Innovator Awards

2016

 

Reza Abdi, MD

New hope for trauma patients with severe burn injuries

 

 

 

 

 

Mike Weaver, MD

21st Century Tools to Measure Bone Healing

 

 

 

 

 

2015

 

Edward Caterson, MD

Healing injuries in the traumatized extremity: Protection, decontamination, and regeneration

 

 

 

 

 

Omid Farokhzad, MD

Development of Nanomedicines for the Prevention of Osteomyelitis and Promotion of Bone Healing and Regeneration Post-Orthopedic Trauma Surgery

 

 

 

 

Bohdan Pomahac, MD

Preservation of amputated limbs for replantation and/or transplantation

 

 

 

 

 

Su-Ryon Shin, PhD

Bioprinted pre-vascularized muscle constructs for limb regeneration and transplants

 

 

 

 

 

2014

 

Matthew J. Carty, MD

Recovering Limb Function: A New Surgical Approach for the 21st Century

 

 

 

 

 

George Dyer, MD

Repairing Large Traumatic Fractures: Using Silk-Based Orthopedic Implants to Promote Healing

 

 

 

 

 

Indranil Sinha, MD

Using Stem Cells to Regenerate Injured Muscle

 

 

 

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