Project Title: Stop the Stigma! Trauma-Informed Care for Patients with Large Bodies

Abstract: Bullying. Shaming. Discrimination. People with large bodies encounter anti-fat bias and weight stigma in nearly every aspect of their lives – including in the offices of well-meaning medical professionals.

Doctors, nurses, and clinic staff who are unaware of the trauma resulting from lifetime experiences of anti-fat bias and internalized stigma may unintentionally retraumatize patients, which can lead to poorer physical and mental health outcomes for this vulnerable population. Unconscious attitudes among health care providers about large-bodied patients can undermine patient-provider trust and result in communication failures and misdiagnosis. When patients perceive that clinicians are overly focused on weight loss, this perception can ignite fear of mistreatment which can lead to decreased healthcare engagement such as missed preventive screenings and deferred treatment for optimal health maintenance.

Despite the detrimental effects that these biases can have on health outcomes, medical professionals receive minimal instruction on the science of weight management during their training. We see addressing the gap in clinical knowledge, which encompasses understanding of the impact of anti-fat bias on patients, as an importance opportunity to enhance health equity for millions of patients.

Watch 2023 recap.

Ahmed Elzoghby, PhD

Project Title: Nano-Engineering Turns Cancer Cell Friends Into Foes

Abstract: Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive and deadliest forms of cancer. Although immunotherapy — drug treatments that enhance the immune system’s ability to detect and fight cancer — has been successfully used to treat many types of solid tumors, challenges limit their success in PDA. In PDA, we see a lot of one kind of cell, known as fibroblasts, around the site of the tumor. These cancer-associated fibroblasts (CAFs) may act like a shield, protecting pancreatic cancer cells in the tumor core from the effects of immunotherapy. We think CAFs play a major role in PDA resistance to immunotherapy.

First, CAFs secrete substances that suppress the activity of immune cells that could otherwise hunt and destroy cancer cells. Second, this shield prevents immune cells from infiltrating the tumor core. Third, CAFs wrap around blood vessels, preventing nanomedicines from reaching their cancer cell targets.

Finally, CAFs secrete exosomes, or “tiny packets of materials,” that internalize easily into the neighboring cancer cells to help them grow and thrive. Given all the advantages that CAFs may provide for cancer cells, we urgently need a way to target CAFs and reprogram the protective shield before we go after cancer cells.

Watch 2022 recap.

Victor Pui-Yan Ma, PhD

Project Title: Reimagining Treatment for Vision loss/Blindness

Abstract: Glaucoma is a leading cause of irreversible blindness and more than 80 million patients are suffering. Currently, there is no cure for glaucoma, and early diagnosis and standard prevention cares only help slow the progression of vision loss. Given its prevalence, there is thus an urgent clinical need to develop new treatment modalities for tackling this disease. Glaucoma is considered as a neurological disease, where a highly specialized type of nerve cells responsible for communicating information between the eye and brain died/damaged throughout the lifespan and cannot be replenished. Looking in the Nature, many animals such as zebrafishes and tetrapods have the ability to repair/regenerate their eyes after injury. In comparison, humans have very limited regenerative capacity. My lab has been working on rejuvenating the regenerative response of human body using small molecule compounds. We previously discovered that small molecule cocktails can unlock the potential of ear cell regeneration and this strategy is being clinically tested for treatment of hearing loss. Here, we propose to test a series of rejuvenating cocktails to restore the regenerative potential of a special type of eye cells called Muller Glia (MG), which can generate all the functional nerve cells in damaged eyes of zebrafishes, but not in mouse and human. We will first test our designed cocktails using mouse MG cells, aiming to convert them to back to a younger state where they have the capability to grow into other functional nerve cells in the right place at the right time. We will also design drug delivery strategies for long-acting delivery of these cocktails into the eye, with a goal of reducing injection frequency to improve the quality of life of patients. This project, if successful, will have untapped potentials in treating eye diseases resulting from the loss/damage of nerve cells.

Peter Novak, MD, PhD

Project Title: Detection of Small Fiber Neuropathy by Artificial Intelligence from Skin Pictures

Abstract: Damage of small nerves termed “small fiber neuropathy” is very common affecting millions of people worldwide and accompanies diabetes and COVID-19 disease. The neuropathy is causing disabling burning pain and dysautonomia such as dizziness with standing, brain fog, fatigue, constipation, too much or too little sweating. The detection of nerve damage is complicated and not widely available, it requires either skin biopsy or specialized equipment and training. This project provides effective solution for limited availability of detection of nerve damage. Using skin pictures obtained from a regular smart phone, the project uses deep machine learning to extract feature from pictures that segregate patients with and without nerve damage. Deep machine learning is a form of artificial intelligence which can be trained to extract patterns from complex pictures. The proposal uses the fact that nerves control skin properties such as elasticity and texture, which will be affected by nerve loss. The deep machine learning will be trained using pictures from skin-biopsy proven nerve damage. Once the artificial intelligence will achieve high diagnostic accuracy, the trained system will be transferred to smart phones. Most of smart phones have sufficient capacity to acquire and process the image, thus to make diagnosis. The project allows detection of nerve damage using regular smart phones instantly at the physician office or remotely using internet.

Natalie Artzi, PhD

Project Title: Training an Immuno-Army to Fight Childhood Brain Cancer

Abstract: Brain tumors or gliomas, are the most common and most fatal childhood cancers in the U.S. Gliomas are treated with surgery and chemotherapy but because it is impossible to remove/kill all of the tumor cells, the cancer always comes back. Molecules that work by activating the immune system are known as immunotherapy. Immunotherapy can be used to “wakeup” the immune system and tell it to destroy cancer cells. The aim of this project is to develop a network of polymer chains—a hydrogel—that serves as a local depot for the delivery of multiple immunotherapies, and can be injected directly into the brain after surgery to stop the tumor from growing and from recurring.

Morteza Mahmoudi, PhD

Project Title: Engineered Nanofribrous Scaffold for Wound Healing Applications.

Abstract: Epidemiological studies suggest that more than globally 550 million people will suffer from diabetes by 2030. As a quarter of these diabetic patients is expected to develop diabetic wounds (e.g., foot ulcers) during their lifetime, there is an urgent need for development of new healing materials to prevent clinical complications. To help achieving the optimal healing environment and protect patients against major clinical implications, the proposed study seeks to develop a bio-inspired engineering approach to prepare scaffolds not only for treatment chronic diabetic wounds but also for healing of wide range of non-diabetic wounds including injury and bedsores.

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.

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.

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.

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.

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.

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.