Fred Hutch researchers receive prestigious R01 research grants

Two Fred Hutch Cancer Center researchers were recently awarded coveted R01 grants from the National Institutes of Health (NIH). 

Katrina Ortblad, ScD, MPH, assistant professor in the Public Health Sciences Division, received a five-year award totaling $3.8 million from the National Institute of Mental Health (NIMH), one of the 27 institutes and centers that make up the NIH. Her award will support research conducted with a co-principal investigator on optimizing HIV prevention care in Kenya. 

Jingyi Jessica Li, PhD, professor and program head of the Biostatistics Program, and professor in the Herbold Computational Biology Program, both in the Public Health Sciences Division, received a four-year award totaling $2.4 million from the National Human Genome Research Institute (NHGRI) for a project to develop a computational tool that ensures that analyses of single-cell and spatial “omics” data are reliable when there is no way to create experimental replicates. Li holds the Donald and Janet K. Guthrie Endowed Chair in Statistics.

The R01 is considered the most prestigious of the research grants awarded by the National Institutes of Health. Awards are typically valued in the millions of dollars and support a single multi-year research project with potentially far-reaching influence in the life sciences.

“The R01 is a career-defining award,” Ortblad explained. “Especially when you’re a young scientist, it is that sort of stamp of approval that you are a bona fide independent researcher. It's something that you strive for for years. You hear about R01s when you're in training, from the master’s level to your PhD to your postdoc to becoming an assistant professor. So, it's been years of training in the making.”

Optimizing the delivery of HIV drugs in Kenya’s pharmacy system

Growing up in Seattle, Ortblad knew that something called “global health” could be a career path. Living in the shadow of the Gates Foundation during its first years in the early 2000s, Ortblad heard the term often and thought it could be a fascinating path to a meaningful career. “I knew from an early age,” she said. “I thought working [in global health] would be the coolest job ever.”

The award will provide Ortblad and her co-principal investigator, Elizabeth Bukusi, PhD, MPH, a research professor in global health at the University of Washington, support to conduct a project that explores the use of telehealth to optimize delivery of HIV prevention drugs to clients at private pharmacies in Kenya.

Before receiving her R01, Ortblad had applied multiple times — a common experience, especially for up-and-coming scientists looking for their first R01 award. Her R01 came about because a new grant opportunity opened from the NIMH, a notice of funding specifically for research on pharmacy HIV PrEP delivery. PrEP, short for “pre-exposure prophylaxis,” is a type of medicine that can be taken by HIV-negative individuals to prevent HIV acquisition. It was a perfect match for Ortblad’s expertise and research background.

“When I saw this specific notice for funding, I thought, wow, we are very well positioned to write this, so we went for it,” Ortblad said.

Ortblad’s R01 project aims to solve a vexing problem: the fact that individuals at risk of exposure to HIV (the virus that causes AIDS), or who have been recently exposed to the virus, can sometimes fail to receive, or to use, medications that are available to them that can stop the virus from replicating in the body — essentially stopping it in its tracks.

This issue can arise not because of price or supply chains, but because of the very last step of the medication-procurement process: the local clinic that supplies the medication. In Kenya, HIV medications have traditionally been administered at public clinics often supported by international aid programs such as PEPFAR (the President’s Emergency Plan for AIDS Relief, established by President George W. Bush in 2003). However, the opportunity to use the more ubiquitous private pharmacies to distribute HIV prevention drugs could help reach people that do not traditionally use public clinics.

“From the formative research that we've done on private pharmacies, we find that we're reaching a lot more unmarried people,” Ortblad said. “We're reaching a lot more people below the age of 25 that are of a very different demographic than those that you see presenting for PrEP at the public clinics.” 

Reaching as many people as possible is particularly crucial in Kenya, where many people that could benefit from PrEP are not using it. The percentage of HIV-positive people in Western Kenya, where Ortblad has conducted her research, is believed to be up to a quarter of the population.

First approved for use by the U.S. Food and Drug Administration (FDA) in 2012, oral PrEP medications, prescribed for HIV-negative people who are at risk of contracting HIV, were a major step forward in reducing the spread of the virus. The use of PEP (post-exposure prophylaxis) medications, designed to be taken soon after an exposure to HIV and first utilized by health care workers in the 1980s, has also helped to limit the spread of the virus. A significant breakthrough in PrEP delivery occurred in 2025 with the FDA’s approval of the twice-yearly injectable PrEP lenacapavir; Ortblad’s study focuses on improving pharmacy delivery of HIV prevention products, primarily daily oral PrEP and PEP, as other new PrEP products have limited distribution in Kenya due to supply chain shortages and high costs.

In her R01-funded project, Ortblad and Bukusi will evaluate the use of a telehealth provider, such as a remote nurse, to conduct the time-consuming steps of pharmacy PrEP/PEP delivery: HIV risk screening, PrEP/PEP counseling and HIV testing (remote nurses will guide clients through HIV self-testing). The remote nurse will also support interested clients with PrEP/PEP use via a phone texting platform between pharmacy visits. 

The goal of the study is to learn whether this type of intervention increases the initiation and continuation (i.e. refilling) of PrEP or PEP medications compared to standard PrEP/PEP delivery by pharmacy providers, an outcome that could influence how governments scale up and support this novel delivery platform to decrease the spread of HIV. This type of telehealth model could be expanded to other countries, particularly in places where not enough pharmacy providers exist. According to Ortblad, this model could alleviate the strain associated with relying on private pharmacies, which often have only one provider present, to deliver PrEP/PEP with the required protocols.

“One of the biggest challenges that we found to actually delivering this model at the private pharmacies from all our pilot studies is the time that it takes pharmacy providers to conduct the counseling and the HIV testing services associated with PrEP delivery,” Ortblad said. 

Ortblad first began work with her Kenyan colleagues as a result of her post-doctoral research at the University of Washington under Jared Baeten, MD, PhD, now an affiliate professor of global health at UW. 

“They had done a lot of early clinical research on PrEP effectiveness” in Kenya, Ortblad said. “And they were transitioning into implementation research on how you could get people to actually use this drug. It was sort of perfect timing to come in as a postdoc and contribute to some of the projects they had in the implementation science research space. They had incredible Kenyan colleagues and collaborators, and it positioned me really nicely to build off those collaborations.” 

Ortblad’s hope is that by identifying the best strategies to support the delivery of HIV prevention medications at private pharmacies, the rate of HIV infection in Kenya will decrease and the strategies identified could be scaled up in Kenya and expanded to other countries.

Creating in-silico ‘controls’ and ‘replicates’ using statistical techniques

In a scientific experiment, Li explained, “you want to replicate your finding to make sure that it can be observed again and again.” But some results simply cannot be replicated, leading to questions about whether the experimental findings are accurate and reliable, or simply a random occurrence.

In the last 15 years, new techniques to learn how single cells act — such as through sequencing the messenger RNA (mRNA) present in their cytoplasm, which reveals the proteins being manufactured inside the cell — have become popular research tools. Single-cell RNA sequencing, or scRNA-seq, involves the sequencing of mRNA present in only one cell. Another related single-cell experimental technique is known as “spatial omics” (the term “ome,” from which “omics” is derived, refers to the totality of a living system, such as the genome — all genes in an organism). 

Spatial omics techniques provide information on a cell’s location as well as the structure of the tissue where the cell is found. The technique holds the promise to eventually visualize a cell’s environment in three dimensions — a critical insight for understanding a cell’s structure and function in the body.

“But for single cell and spatial omics [experiments] that involve sequencing, you disrupt the biological material and so you cannot measure it again,” Li said. “And if you believe every cell is different, you [also] cannot measure it again. So how can we ensure that our results are reproducible, and not just random?”

Li’s R01 project aims to solve this problem. She will employ a statistical technique to create “in-silico” pseudo-replicates: data generated not from an in-vivo (inside a living organism) or an in-vitro (inside a laboratory environment, as in a cell culture) study, but from a computer. (The term “in-silico” refers to the silicon contained in computer chips.) 

Through this technique, Li will generate in-silico negative and positive “controls” or “pseudo-replicate” data (real data injected with noises, based on observations of experimental data) from the single-cell data generated through scRNA-seq or spatial omics studies to test the experimental data for validity.

Previously, Li received an R01 to use statistical techniques to help infer the accuracy of mRNA sequencing when the only type of data available from such experiments was partial, meaning that only fragments of whole RNA transcripts could be sequenced at a time. While her second R01 focuses on a larger issue of ensuring the validity of single-cell experimental techniques, the thread connecting her projects is one universal to all scientists: ensuring that experimental data and the analyses of those data are accurate. It is a testament to Li’s vision and scientific promise that both of her R01s were funded on her first try, a rare and notable outcome that she referred to as being “unbelievably lucky.”

Li aspires to build an easy-to-use interface that can be widely used by life scientists to generate in-silico data controls and replicates to better ensure that their experimental data analyses are valid. 

“We are envisioning that our users will be computational scientists who do data analysis,” she explained. “They can use [the data generated by our platform, such as negative controls and pseudo-replicates] together with their [experimental] data to run a computational pipeline. Our hope is that these data sets will provide a safety guarantee for them to see how they can trust the results they see from their real data.”