Uncovering biological properties of extracellular vesicles, which play a vital role in how cells communicate, and understanding how sex hormones drive behavior and development are two areas that the new cohorts of Allen Distinguished Investigators will research, thanks to over $10 million in funding from the Paul G. Allen Family Foundation. The 18 researchers will develop technologies, design approaches, and uncover insights into fundamental areas of human biology. 

2023 Allen Distinguished Investigators

•  Kenneth Witwer, Ph.D., Johns Hopkins University School of Medicine 
• Angela M. Zivkovic, Ph.D., University of California, Davis 
• Wyatt N. Vreeland, Ph.D., National Institute of Standards and Technology 
• Shinichi Kano, M.D., Ph.D., University of Alabama at Birmingham 
• Andrew Chisholm, Ph.D., University of California San Diego 
• Ann Wehman, Ph.D., University of Denver 
• Marni D. Boppart , Sc.D., University of Illinois at Urbana-Champaign 
• Stephen A. Boppart, M.D., Ph.D., University of Illinois at Urbana-Champaign 
• Annegret Falkner, Ph.D., Princeton University 
• Stephanie Correa, Ph.D., University of California, Los Angeles 
• Ed van Veen, Ph.D., University of California, Los Angeles 
• Boris Novakovic, Ph.D., Murdoch Children’s Research Institute 
• Ada Cheung, Ph.D., University of Melbourne 
• Rachel Davey, Ph.D., Department of Medicine, Austin Health, University of Melbourne  
• Musa M. Mhlanga, Ph.D., Radboud Institute for Molecular Life Sciences 
• Mijo Simunovic, Ph.D., Columbia University 
• Elham Azizi, Ph.D., Columbia University 
• José L. McFaline-Figueroa, Ph.D., Columbia University 

The Paul G. Allen Family Foundation will award $1.5 million to seven research projects which 18 researchers will lead. Together, these awards represent a total of approximately $10.5 million in funding from the Foundation, as recommended by The Paul G. Allen Frontiers Group, to support cutting-edge, early-stage research projects that promise to advance the fields of biology and medicine. The seven awarded projects were selected from open calls for proposals in two fields: extracellular vesicles and sex hormones. When considering funding areas, The Frontiers Group looks for emerging fields where an investment could be catalytic to advance scientific progress—not just for awardees, but for all in that particular field.  

 “Our two newest cohorts of Allen Distinguished Investigators are using innovative technologies and unprecedented ambition to pioneer new frontiers in the fields of sex hormones and extracellular vesicles. These discoveries have the potential to not only change and challenge our current understanding of basic biological principles but also are poised to reveal significant implications in human health.” said Kathy Richmond, Ph.D., M.B.A., Executive Vice President and Director of the Frontiers Group and the Office of Science and Innovation at the Allen Institute. 

Meet the New Allen Distinguished Investigators Researching Extracellular Vesicles

Extracellular vesicles hold huge promise as a means of therapeutic delivery; however, their diversity and a lack of understanding of their basic biology are hindering progress. This cohort seeks to elucidate fundamental principles of the biology of extracellular vesicles in a variety of contexts, including the development of technologies to better visualize and track them in living organisms.

In this project, researchers will investigate a recently recognized feature of extracellular vesicles (EVs) known as the “EV corona,” a layer of molecules that may imbue EVs with specialized properties. Researchers will use advanced analytical methods to detect and identify the molecules of the EV corona and map them with unprecedented detail. Additionally, they will bioengineer EVs by linking their surfaces directly to specific proteins of the corona to disguise the EVs from the body’s immune system. Doing so is important because EVs can be used to diagnose and treat diseases; however, exogenous EVs may be attacked by the immune system before their therapeutic benefits can be exerted. Allowing them to remain in the body longer could lead to better therapies and treatments for disease.

A significant challenge with treatments for brain disorders is the lack of efficient drug delivery systems into the brain. As part of this research project, Shinichi Kano and his team will examine the mechanisms by which extracellular vesicles (EVs) can cross the blood-brain barrier to gain entry into the brain and identify the core molecules of EVs and their recipient cells that allow them to influence neurons. The proposed study will reveal new insights into the foundational mechanisms by which EVs act within the body. The study will also generate extensive datasets that could contribute to developing novel EV-inspired drug delivery systems for the brain.

In this project, researchers will examine the role extracellular vesicles (EVs) play in helping neurons maintain their shape. Failure to maintain neuronal shape can lead to impaired brain function or neurodegeneration. Changes in the function of proteins that regulate EV release can restore healthy neuron shape in animals, suggesting regulation of EVs maintains neuronal shape. Moreover, researchers have found that such EV regulators affect the shape of other cell types such as skin or germ cells. This project will take a multidisciplinary approach including microscopy, protein design, and genetics to learn how these factors affect cellular shape in worms and mammals and develop novel probes for EV-related lipids. The results may reveal how EVs contribute to neuronal resilience, with implications for brain health. 

Researchers Marni and Stephen Boppart will use next-generation, multimodal, nonlinear optical microscopy techniques to obtain real-time, dynamic images of EVs in living tissues and use this advanced platform to identify the role EVs play in human aging. Recent studies suggest that aged cells secrete EVs carrying materials that promote aging throughout the body. However, no tools currently exist to effectively study EVs in the natural tissue microenvironment. This project will not only yield a powerful microscopy platform that will provide the first visualization of EV dynamics within a complex living tissue microenvironment but will also provide new insight regarding fundamental EV biology in the context of multiple conditions, including aging and disease. 

Meet the Allen Distinguished Investigators Researching Sex Hormones

Researchers in this cohort are uncovering the cellular and molecular actions of sex hormones outside of reproduction and reproduction-related development. Their work addresses a key need to deepen our understanding of how sex hormones affect many biological processes. These new discoveries have the potential to impact human health, including diagnostics and treatment.

This project seeks to understand the relationship between hormones, neural activity, and behavior. Researchers will develop an all-optical platform for recording hormone-related signaling in the brain that can be combined with existing optical methods for recording neural activity. The platform will allow researchers to directly observe the relationship between hormone effects and brain state. This work represents a collaborative effort between three labs with extensive experience in molecular tool development, longitudinal imaging and computation, and neuroendocrinology. The collaboration will improve the ability to track hormone signaling across the lifespan in order to shed light on the diverse roles of sex hormones in health and disease. 

There are well known differences between how male and female immune systems function. For example, females show lower COVID-19 mortality and lower rates of cardiovascular disease than males, but have higher rates of auto-immune disease. It is also known that sex hormones can influence immune function, but how they do this in the context of infection and inflammatory disease is unclear. In this project, researchers will investigate how sex hormones (estradiol and testosterone) change the immunity of transgender individuals undergoing gender affirming hormone therapy. This longitudinal approach will allow researchers to study the action of sex hormones beyond the population level, and to dive deeper into how circulating sex hormones affect individual immune responses. Insights from this study could be used to improve health outcomes for transgender individuals and provide greater understanding into the action of sex hormones on immunity more generally. 

How sex hormones influence organ development in the early embryo is not fully understood, but it is believed that they play an important role as a signaling molecule in early development. In this project, researchers will develop an in vitro platform that combines stem cell models of human development, high-throughput genome editing at the single-cell level, and novel machine learning approaches to precisely define how sex hormones participate in cellular differentiation during organ development. This new embryomimetic platform has the potential to reveal unexpected connections between sex hormones and biochemical signaling, which could integrate sex hormone signaling within the broader efforts of mapping the human body. 

The Allen Distinguished Investigator program was launched in 2010 by the late philanthropist Paul G. Allen to back creative, early-stage research projects in biology and medical research that would not otherwise be supported by traditional research funding programs. Including the new awards, a total of 130 Allen Distinguished Investigators have been appointed during the past 12 years. Each award spans three years of research funding.