Current and Past Sprout Projects
Treatment of hypertension using novel chemogenetic approach
World-wide, cases of hypertension have increased from 594 million to 1.13 billion between 1975 and 2015, with 20% of cases being refractory to current therapies. This defines a major health crisis since uncontrolled blood pressure dramatically increases the risk for stroke, heart attack, heart failure, and even death. Heightened sympathetic drive, defined as overactivity of the sympathetic neurons that directly communicate with peripheral organs, precedes and drives the development of hypertension. Current drug treatments lower blood pressure by targeting a variety of specific pathways in organs downstream of these neurons. These treatments successfully lower blood pressure in 80% of the population; however, the remaining 20% is drug-resistant with no effective drugs to lower their blood pressure. This project proposes a new therapeutic product that inhibits the activity of the sympathetic neurons driving hypertension allowing for the treatment of drug-resistant hypertension.
Small-molecule control of kinase-phosphatase interactions
Kinase inhibitors have emerged as a major drug class in the treatment of cancer over the past twenty years. However, a major limiting factor for kinase targeted therapies is achieving specificity and potency of inhibition. This invention focuses on ATP competitive kinase inhibitors that can leverage phosphatase synergy. They impact inhibitor potency and pharmacokinetics. These discoveries propose a new strategy for assaying and refining kinase inhibition that includes how the inhibitor interacts with phosphatases. Specifically, the project posits a scalable and general method for profiling kinase inhibitor/phosphatase interactions. In parallel, it will identify novel inhibitors of p38 MAP Kinase that optimize these effects, which may yield more potent and specific inhibitors of p38 for treatment of cancer and neurodegeneration.
Solid-state MOST system utilizing 2+2 cycloaddition
Sustainable energy solutions and alternatives are becoming increasingly critical as the realities of climate change affect everyday life. This project proposes to leverage the sun as a renewable resource by using novel, photo-active materials to absorb sunlight and convert it into stored, usable energy: Molecular Solar Thermal Energy Storage (MOST). Our material sets a new standard in photoswitching organic materials due to its ability to change colors and even transparent when exposed to sunlight. Using MOST, one could coat everyday objects such as windows, creating not only aesthetic, customizing designs but also an energy-efficient method to store solar energy, convert it to heat, and emit it in absence of sunlight. This proposal aims to use MOST to facilitate efficient capture, storage, and release of solar energy: envision a color-changing window coating for both residential and commercial applications, respectively.
CaMKII inhibition as an alternative for different cancer treatments
Nearly two million Americans were diagnosed with cancer in 2022, making it the country's second leading cause of death. Cancer is a disease caused by the aberrant replication of cells as a result of malfunctioning enzymes within the cell that eventually affect and recruit neighboring, healthy cells. Kinases are a well-studied group of enzymes associated with cancer-related illness and are involved in diverse signaling and metabolic pathways. Dramatic shifts in kinase activity result in undesired, often harmful protein interactions. Here, we propose the development of a CaMKII kinase inhibitor as a potential cancer treatment. CaMKII kinase is an accepted cancer diagnostic marker with no current FDA-approved inhibitors available.r cancer and arrhythmia diagnosis. This project aims to identify and validate specific CamKII inhibitor candidates for potential cancer therapy use.
Development of galectin inhibitors
Galectins are a family of 12 carbohydrate binding proteins with similar binding affinities to many lactose-based sugars. They are implicated in numerous biological diseases including fibrosis, cancers, vision impairment inflammation, diabetes, and related conditions making them a prime target for novel therapy development.
Whereas traditional medicinal chemistry design, synthesis, and testing has been the predominant strategy for galectin inhibitor design, this drug development approach will use a directed evolution method that was developed in-house. Leveraging the mRNA display of glycopeptides, the team can design inhibitors with an improved nanomolar binding affinities and at least a 100-fold selectivity versus off-target galectins. The initial target will be galectin-1, which is implicated in liver, pancreatic, and pulmonary fibrosis, melanoma, head and neck squamous cell carcinoma, and lung, kidney, and bladder cancers.
Machine learning methods for scoring telephone assessments of reaction time
One in 9 Americans over the age of 65 has Alzheimer’s Disease (AD). As a result of emerging symptoms being mistaken for mental health or sleep disorders, AD is frequently misdiagnosed. Sadly, treatment is less successful when a diagnosis is delayed. Due to the delay between noticeable changes in brain health and the onset of memory loss symptoms, recent advances in AD research are investigating the viability of a detection method at the preclinical stage to allow for early diagnosis and therefore treatments to slow or stop the disease. The importance of cognitive assessments in detecting early indicators of cognitive decline and AD is becoming more widely acknowledged.
The Stop and Go Switch Task (SGST), created by Dr. Lachman, uses reaction time in trials requiring attention switching and inhibitory control to evaluate executive function. It is the only test of its kind that is conducted over the phone. This project is a platform that automates this test to make it more adaptable. This research tool will ultimately serve as a catalyst for research in cognitive aging and AD risk, leading to early interventions and improved treatment efficacy.
Synthetic single-domain antibodies function as an important weapon against infections and diseases. Currently, the production and screening of synthetic, single-domain antibody libraries often rely on animals, phage display or yeast-based platforms. Traditionally, these reagents are sourced from biological sources by injecting antigens into camelid species and then harvesting the immunoglobulins. All the current methodologies have biochemical and genetic limitations. This team seeks to develop a platform for synthetic single domain antibody production based on expression and selection in intact bacteria. Use of this approach is faster and more robust than existing approaches and is adoptable by any user that has experience in basic molecular biology.
A new antiviral avenue: Targeting Fe-S clusters in viral proteases
Viral polyproteins contain embedded proteases that act as molecular scissors to release the mature non-structural proteins (NSPs) that sustain the replication and transcription of the viral genome. Therefore, these proteases have attracted attention as ideal therapeutic targets at the early onset of infection. The role of these proteases is not restricted to the cleavage of viral polyproteins, but also to modulate activities that intercept the function of host proteins, ultimately derailing the host immune defense. Although approaches exist for inhibiting the catalytic domain of various viral proteases, current methods are of variable efficacy and can easily lead to the rise of resistance mutations. Furthermore, the exact molecular mechanism by which these inhibitors halt protein function is often sparsely understood. This project aims to study metallofactors, their physiological relevance and their effect on protease activities, allowing for therapeutic approaches with general applicability as they broadly target core proteins that facilitate viral replication and transcription.