In the past two decades, therapeutics have rapidly evolved to encompass a diverse range of biopharmaceuticals presenting new challenges and opportunities for global health. While, biologics offer unparalleled target specificity, dramatically increasing potency, their complex chemical structures create significant hurdles to administration and accessibility. The path from an active pharmaceutical ingredient (API) to a clinical therapeutic requires overcoming three key challenges: (1) biological barriers (biodistribution & pharmacokinetics), (2) human factors (storage conditions & administration), and (3) global access (cold-chain distribution & cost effective scale-up). As a result, modern biologic drugs are all a product of highly engineered formulations whether it is a monoclonal antibody (mAb) stabilized by surfactant excipients, an mRNA vaccine encapsulated in a lipid nanoparticle (LNP), or a GLP-1 agonist peptide formulated as an oral tablet with a permeation enhancing surfactant. Looking towards the opportunities and inspired by the unparalleled global impact of vaccines, the next generation of formulation technologies, which precisely orchestra spatial and temporal delivery of biologics in vivo, are unlocking new immunotherapies to combat devastating neglected tropical diseases (NTDs) impacting more than 1 billion people across the globe. My research program is uniquely poised to overcome these challenges and take advantage of  these opportunities: First, we will improve accessibility of biopharmaceuticals with novel formulation approaches, leveraging my extensive background in excipient engineering, and second, we will position ourselves at the intersection of drug delivery and immunotherapy, by exploiting cutting-edge immunoengineering platforms to create prophylactic measures against critical NTDs (snakebite envenoming and helminth infections).

The therapeutic landscape for human health has changed dramatically over the past decade, with the rise of monoclonal antibodies as immunomodulators treat cancer and inflamatory diseases, nucleic acid (mRNA) vaccines to prevent infectious diseases, and revolutionary peptide drugs to treat diabetes, obesity, cancer, and even cardiovascular diseases. While these biopharmaceuticals have shown incredible promise, their global impact is severely limited due to poor accessibility, as a result of stringent cold storage requirements, and burdensome administration regimens. During my postdoctoral fellowship, I have demonstrated that copolymer surfactant excipients can be rationally designed and optimized to improve global access to soluble injectable peptides (insulin) and monoclonal antibody therapeutics. However, for nucleic acid therapeutics and oral drug delivery, globally accessible formulations are still lacking. To expand access, we will engineer new technologies to eliminate the cold-chain for nucleic acid therapeutics (such as mRNA vaccines) and develop novel copolymer permeation enhancing surfactants to enable oral delivery of peptide drugs (eliminating the need for burdensome injections).

What do snake bites, bee stings, grass pollen, peanuts, and tapeworms have in common? All of these foreign substances trigger allergic (Type 2) immune responses. Given this broad range of threats it remains a mystery which of these foreign substances the Type 2 immune response evolved directly to target. What we do know is that the Type 2 immune response is characterized by a coordinated effort between several cell types to elicit a tissue level response to foreign invaders known as "weep and sweep". 

To-date scientists investigating these tissue level immune responses have been limited in their ability to understand how spatial and temporal exposure impact the development of productive Type 2 immunity. In the best cases Type 2 immunity can protect us from parasitic worms or even snake bites, and in the worst case exposure to a benign food can trigger deadly anaphylactic shock. In the case of infection by a parasitic worm the invading organism persistently exerts chemical and physical stress on an infected tissue for days to weeks, leading to a productive weep and sweep response. Mimicking the continuous stimulation of the immune system and mechanical stress on the tissue environment is vital to replicating this beneficial case of Type 2 immunity, but until recently we lacked the necessary biomaterial tools to mimic these conditions. Now with dynamic, injectable, long lasting depot, technologies we can systematically isolate and replicate key aspects of these types of infections. No parasitic worm required! 

Utilizing new biomaterial strategies to productively isolate unique Type 2 immune pathways, we will be able to harness this powerful Type of immunity to provide protection against neglected tropical diseases, such as parasitic worm infections and snakebite envenoming.