Stanford scientists use NIH grants to accelerate research on arthritis and lupus

Stanford was recently awarded both the Leadership Center grant and a site grant for what is officially named the Accelerating Medicines Partnership in Rheumatoid Arthritis and Lupus Network. PJ Utz, MD (professor, immunology and rheumatology) heads the Leadership Center with Dr. V. Michael Holers from the University of Colorado. He also co-leads the Stanford site with William H. Robinson, MD, PhD (associate professor, immunology and rheumatology).

In announcing the Leadership Center and the site award, NIH Director Francis S. Collins, MD, PhD, said: "These awards represent the first phase of an unprecedented approach to identify pathways that are critical to disease progression in rheumatoid arthritis and lupus. Insights gained from this effort hold the promise of enhancing quality of life for patients and family members affected by these and other devastating autoimmune diseases." 

There are a number of unusual aspects to this Network grant. For one thing, it is a public/private partnership with participation by both drug companies and foundations in addition to the NIH and academic research centers. This makes sense to Utz: “In rheumatoid arthritis alone, it is predicted that there are going to be 25 drugs on market by 2025, many of which will be generic at that point. So there is going to be a huge armamentarium of drugs from which to choose. Then the question becomes, how do we choose among them? The companies are looking for new targets that might be ‘druggable’ and for subsets of patients for whom certain drugs might be appropriate.”

We look at this as a great opportunity that could transform how university researchers partner with industry.  – PJ Utz

This is where a second unusual aspect of this grant comes in. The Network, according to the NIH, aims to “transform the current model for identifying and validating the most promising biological targets” for developing new drugs for rheumatoid arthritis (RA) and lupus. As the two autoimmune diseases are similarly dysregulated in ways that cause inflammation and damage tissues, the hope is that refocusing research on tissue will advance the discovery of new therapies.

This fits well with the plans of the Stanford group. As Utz says, “the difference between this study and pretty much most studies that have been done in the literature is that this one focuses on the tissue itself. Much of my work and that of Bill Robinson and Mark Davis, PhD (professor, microbiology and immunology) has been to study blood or synovial fluid from patients with these diseases because it is easy to obtain and easy to study.  Having taken that field about as far as it can go, the real challenge is to gain access to the diseased tissues themselves and see if we can identify new drug targets, and find better ways to diagnose and to target patients for specific therapies.”


“The methodologies that the different sites are using are really cool, cutting edge. Our site brings to bear a variety of technologies, almost all of which were invented here at Stanford. Some examples are listed below.

Technologies developed @ Stanford

  1.  CyTOF, developed by Garry Nolan, PhD (professor, microbiology and immunology), which is a way of looking at between 50 and 100 markers on single cells using mass spectrometry coupled to flow cytometry. Nolan is the world expert in this technology.
  2.  MIBI, or multiplexed ion beam imaging, also developed by Nolan, is similar to CyTOF in some ways and can be used to study tissue sections.
  3.  Bill Robinson has pioneered repertoire analysis and creates monoclonal antibodies.
  4.  Mark Davis, PhD (professor, microbiology and immunology), invented tetramers for looking at specific T cell responses, and is leading efforts at Stanford for characterizing the entire human immune system.
  5.  Atac-seq is a method developed by Howard Chang, MD, PhD (professor, dermatology), and William Greenleaf, PhD (assistant professor, genetics), which allows groups to look at epigenetics and genetics in an unparalleled way.
  6.  Steve Quake, PhD (professor, bioengineering and applied physics), invented the Fluidigm chip and has led many other bioengineering advances such as single cell RNA sequencing, which allows groups to look at single cells and identify genes that are turned on or turned off.”

A third element that is new to this grant is the agreement among all the partners that the data and the analyses will be made accessible broadly to the biomedical research community. The partners see this as a way to significantly increase the speed of drug development.

Utz further explains that “companies don’t have the ready access to tissues that universities have. Academic researchers tend to protect the tissues that they harvest and work with. This public/private partnership is a way for the companies to gain access to tissues they wouldn’t ordinarily get and to partner with universities to study the samples using the most advanced methods available. It is a win-win for companies, universities, NIH, and hopefully for patients.

With such a huge mission, a large group of extraordinarily talented researchers (Utz described it as “the dream team of RA and lupus research”), and a substantial amount of NIH funding, how does Utz define success?

“By the end of the 5 years, we should have produced huge datasets in lupus and RA, identified pathways and molecules, and set up an infrastructure that assures that this doesn’t end in 5 years.”

First-year funding arrived October 1. The clock has started.