The Journey of a Homegrown Stem Cell Research All-Star

Nothing makes a professional sports team prouder than its homegrown talent. Training and mentoring a promising, hard-working athlete who eventually helps carry the team to a championship can lift the spirits of an entire city.

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Brian Fury

Here at CIRM, we hold a similar sense of pride in Brian Fury, one of our own homegrown all-stars. Nearly a decade ago, Brian was accepted into the inaugural class of CIRM’s Bridges program which provides paid stem cell research internships to students at California universities and colleges that don’t have major stem cell research programs. The aim of the program, which has trained over 1200 students to date, is to build the stem cell work force here in California to accelerate stem cell treatments to patients with unmet medical needs.

A CIRM full circle
Today, Brian is doing just that as manager of manufacturing at the UC Davis Institute for Regenerative Cures (IRC) where he leads the preparation of stem cell therapy products for clinical trials in patients. It was at UC Davis that he did his CIRM Bridges internship as a Sacramento State masters student back in 2009. So, he’s really come full circle, especially considering he currently works in a CIRM-funded facility and manufactures stem cell therapy products for CIRM-funded clinical trials.

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Gerhard Bauer

“Many of the technicians we have in the [cell manufacturing] facility are actually from the Bridges program CIRM has funded, and were educated by us,” Gerhard Bauer, Brian’s boss and director of the facility, explained to me. “Brian, in particular, has made me incredibly proud. To witness that the skills and knowledge I imparted onto my student would make him such an integral part of our program and would lead to so many novel products to be administered to people, helping with so many devastating diseases is a very special experience. I treasure it every day.”

“It sustains me”
Brian’s career path wasn’t always headed toward stem cell science. In a previous life, he was an undergrad in computer management information systems. It was a required biology class at the time that first sparked his interest in the subject. He was fascinated by the course and was inspired by his professor, Cathy Bradshaw. He still recalls a conversation he had with her to better understand her enthusiasm for biology:

“I asked her, ‘what is it about biology that really made you decide this is what you wanted to do?’ And she just said, ‘It sustains me. It is air in my lungs.’ It was what she lived and breathed. That really stuck with me early on.“

Still, Brian went on to earn his computer degree and worked as a computer professional for several years after college. But when the dot com boom went bust in the early 2000’s, Brian saw it as a sign to re-invent himself. Remembering that course with Professor Bradshaw, he went back to school to pursue a biology degree at Sacramento State University.

On a path before there was a path
Not content with just his textbooks and lectures at Sac State, Brian offered to volunteer in any lab he could find, looking for opportunities to get hands-on experience:

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Brian at work during his Sacramento State days.

“I was really hungry to get involved and I really wanted to not just be in class and learning about all these amazing things in biology but I also wanted to start putting them to work. And so, I looked for any opportunity that I could to become actively involved in actually seeing how biology really works and not just the theory.”

This drive to learn led to several volunteer stints in labs on campus as well as a lab manager job. But it was an opportunity he pursued as he was finishing up his degree that really set in motion his current career path. Gerhard Bauer happened to be giving a guest lecture at Sac State about UC Davis’ efforts to develop a stem cell-based treatment for HIV. Hearing that talk was an epiphany for Brian. “That’s really what hooked me in and helped determine that this is definitely the field that I want to enter into. It was my stepping off point.”

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Brian Fury (center) flanked by mentors Gerhard Bauer (left) and Jan Nolta (right)

Inspired, Brian secured a volunteering gig on that project at UC Davis – along with all his other commitments at Sac State – working under Bauer and Dr. Jan Nolta, the director of the UC Davis Stem Cell Program.

That was 2008 and this little path Brian was creating by himself was just about to get some serious pavement. The next year, Sacramento State was one of sixteen California schools that was awarded the CIRM Bridges to Stem Cell Research grant. Their five-year, $3 million award (the total CIRM investment for all the schools was over $55 million) helped support a full-blown, stem cell research-focused master’s program which included 12-month, CIRM-funded internships. One of the host researchers for the internships was, you guessed it, Jan Nolta at UC Davis.

Good Manufacturing Practice (GMP) was a good move
Applying to this new program was a no brainer for Brian and, sure enough, he was one of ten students selected for the first-year class. His volunteer HIV project in the Nolta lab seamlessly dovetailed into his Bridges internship project. He was placed under the mentorship of Dr. Joseph Anderson, a researcher in the Nolta lab at the time, and gained many important skills in stem cell research. Brian’s project focused on a stem cell and gene therapy approach to making HIV-resistant immune cells with the long-term goal of eradicating the virus in patients. In fact, follow on studies by the Anderson lab have helped lead to a CIRM-funded clinical trial, now underway at UC Davis, that’s testing a stem cell-based treatment for HIV/AIDs patients.

After his Bridges internship came to a close, Brian worked on a few short-term research projects at UC Davis but then found himself in a similar spot: needing to strike out on a career path that wasn’t necessarily clearly paved. He reached out to Nolta and Bauer and basically cut to the chase in an email asking, “do you know anybody?”. Bauer reply immediately, “yeah, me!”. It was late 2011 and UC Davis had built a Good Manufacturing Practice (GMP) facility with the help of a CIRM Major Facility grant. Bauer only had one technician at the time and work was starting to pick up.

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The Good Manufacturing Practice (GMP) facility in UC Davis’ Institute for Regenerative Cures.

A GMP facility is a specialized laboratory where clinical-grade cell products are prepared for use in people. To ensure the cells are not contaminated, the entire lab is sealed off from the outside environment and researchers must don full-body lab suits. We produced the video below about the GMP facility just before it opened.

Bauer knew Brian would be perfect at their GMP facility:

“Brian was a student in the first cohort of CIRM Bridges trainees and took my class Bio225 – stem cell biology and manufacturing practices. He excelled in this class, and I also could observe his lab skills in the GMP training part incorporated in this class. I was very lucky to be able to hire Brian then, since I knew what excellent abilities he had in GMP manufacturing.”

CIRM-supported student now supporting CIRM-funded clinical trials

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Brian Fury suited up in GMP facility

Since then, Brian has worked his way up to managing the entire GMP facility and its production of cell therapy products. At last count, he and the five people he supervises are juggling sixteen cell manufacturing projects. One of his current clients is Angiocrine which has a CIRM-funded clinical trial testing a cell therapy aimed to improve the availability and engraftment of blood stem cell transplants. This treatment is geared for cancer patients who have had their cancerous bone marrow removed by chemotherapy.

When a company like Angiocrine approaches Brian at the GMP facility, they already have a well-defined method for generating their cell product. Brian’s challenge is figuring out how to scale up that process to make enough cells for all the patients participating in the clinical trial. And on top of that, he must design the procedures for the clean room environment of the GMP facility, where every element of making the cells must be written down and tracked to demonstrate safety to the Food and Drug Administration (FDA).

The right time, the right place…and a whole bunch of determination and passion
It’s extremely precise and challenging work but that’s what makes it so exciting for Brian. He tells me he’s never bored and always wakes up looking forward to what each day’s challenges will bring and figuring out how he and his team are going get these products into the clinic. It’s a responsibility he takes very seriously because he realizes what it means for his clients:

“I invest as much energy and passion and commitment into these projects as I would my own family. This is extremely important to me and I feel so incredibly fortunate to have the opportunity to work on things like this. The reality is, in the GMP, people are bringing their life’s work to us in the hopes we can help people on the other end. They share all their years of development, knowledge and experience and put it in our hands and hope we can scale this up to make it meaningful for patients in need of these treatments.”

Despite all his impressive accomplishments, Brian is a very modest guy using phrases like “I was just in the right place at the right time,” during our conversation. But I was glad to hear him add “and I was the right candidate”. Because it’s clear to me that his determination and passion are the reasons for his success and is the epitome of the type of researcher CIRM had hoped its investment in the Bridges program and our SPARK high school internship program would produce for the stem cell research field.

That’s why we’ll be brimming over with an extra dose of pride on the day that one of Brian’s CIRM-funded stem cell therapy products reaches the goal line with an FDA approval.

Cell mate: the man who makes stem cells for clinical trials

When we announced that one of the researchers we fund – Dr. Henry Klassen at the University of California, Irvine – has begun his clinical trial to treat the vision-destroying disease retinitis pigmentosa, we celebrated the excitement felt by the researchers and the hope from people with the disease.

But we missed out one group. The people who make the cells that are being used in the treatment. That’s like praising a champion racecar driver for their skill and expertise, and forgetting to mention the people who built the car they drive.

Prof. Gerhard Bauer

Prof. Gerhard Bauer

In this case the “car” was built by the Good Manufacturing Practice (GMP) team, led by Prof. Gerhard Bauer, at the University of California Davis (UC Davis).

Turns out that Gerhard and his team have been involved in more than just one clinical trial and that the work they do is helping shape stem cell research around the U.S. So we decided to get the story behind this work straight from the horse’s mouth (and if you want to know why that’s a particularly appropriate phrase to use here read this previous blog about the origins of GMP)

When did the GMP facility start, what made you decide this was needed at UC Davis?

Gerhard: In 2006 the leadership of the UC Davis School of Medicine decided that it would be important for UC Davis to have a large enough manufacturing facility for cellular and gene therapy products, as this would be the only larger academic GMP facility in Northern CA, creating an important resource for academia and also industry. So, we started planning the UC Davis Institute for Regenerative Cures and large GMP facility with a team of facility planners, architects and scientists, and by 2007 we had our designs ready and applied for the CIRM major facilities grant, one of the first big grants CIRM offered. We were awarded the grant and started construction in 2008. We opened the Institute and GMP facility in April of 2010.

How does it work? Do you have a number of different cell lines you can manufacture or do people come to you with cell lines they want in large numbers?

Gerhard: We perform client driven manufacturing, which means the clients tell us what they need manufactured. We will, in conjunction with the client, obtain the starting product, for instance cells that need to undergo a manufacturing process to become the final product. These cells can be primary cells or also cell lines. Cell lines may perhaps be available commercially, but often it is necessary to derive the primary cell product here in the GMP facility; this can, for instance, be done from whole donor bone marrow, from apheresis peripheral blood cells, from skin cells, etc.

How many cells would a typical – if there is such a thing – order request?

Gerhard: This depends on the application and can range from 1 million cells to several billions of cells. For instance, for an eye clinical trial using autologous (from the patient themselves) hematopoietic stem and progenitor cells, a small number, such as a million cells may be sufficient. For allogeneic (from an unrelated donor) cell banks that are required to treat many patients in a clinical trial, several billion cells would be needed. We therefore need to be able to immediately and adequately adjust to the required manufacturing scale.

Why can’t researchers just make their own cells in their own lab or company?

Gerhard: For clinical trial products, there are different, higher, standards than apply for just research laboratory products. There are federal regulations that guide the manufacturing of products used in clinical trials, in this special case, cellular products. In order to produce such products, Good Manufacturing Practice (GMP) rules and regulations, and guidelines laid down by both the Food and Drug Administration (FDA) and the United States Pharmacopeia need to be followed.

The goal is to manufacture a safe, potent and non-contaminated product that can be safely used in people. If researchers would like to use the cells or cell lines they developed in a clinical trial they have to go to a GMP manufacturer so these products can actually be used clinically. If, however, they have their own GMP facility they can make those products in house, provided of course they adhere to the rules and regulations for product manufacturing under GMP conditions.

Besides the UC Irvine retinitis pigmentosa trial now underway what other kinds of clinical trials have you supplied cells for?

Gerhard: A UC Davis sponsored clinical trial in collaboration with our Eye Center for the treatment of blindness (NCT01736059), which showed remarkable vision recovery in two out of the six patients who have been treated to date (Park et al., PMID:25491299, ), and also an industry sponsored clinical gene therapy trial for severe kidney disease. Besides cellular therapy products, we also manufacture clinical grade gene therapy vectors and specialty drug formulations.

For several years we have been supplying clinicians with a UC Davis GMP facility developed formulation of the neuroactive steroid “allopregnanolone” that was shown to act on resident neuronal stem cells. We saved several lives of patients with intractable seizures, and the formulation is also applied in clinical trials for the treatment of traumatic brain injury, Fragile X syndrome and Alzheimer’s disease.

What kinds of differences are you seeing in the industry, in the kinds of requests you get now compared to when you started?

Gerhard: In addition, gene therapy vector manufacturing and formulation work is really needed by several clients. One of the UC Davis specialties is “next generation” gene-modified mesenchymal stem cells, and we are contacted often to develop those products.

Where will we be in five years?

Gerhard: Most likely, some of the Phase I/II clinical trials (these are early stage clinical trials with, usually, relatively small numbers of patients involved) will have produced encouraging results, and product manufacturing will need to be scaled up to provide enough cellular products for Phase III clinical trials (much larger trials with many more people) and later for a product that can be licensed and marketed.

We are already working with companies that anticipate such scale up work and transitioning into manufacturing for marketing; we are planning this upcoming process with them. We also believe that certain cellular products will replace currently available standard medical treatments as they may turn out to produce superior results.

What does the public not know about the work you do that you think they should know?

Gerhard: The public should know that UC Davis has the largest academic Good Manufacturing Practice Facility in Northern California, that its design was well received by the FDA, that we are manufacturing a wide variety of products – currently about 16 – that we are capable of manufacturing several products at one time without interfering with each other, and that we are happy to work with clients from both academia and private industry through both collaborative and Fee-for-Service arrangements.

We are also very proud to have, during the last 5 years, contributed to saving several lives with some of the novel products we manufactured. And, of course, we are extremely grateful to CIRM for building this state-of-the-art facility.

You can see a video about the building of the GMP facility at UC Davis here.