Inside Stanford Medicine - October 25th, 2010 - by Krista Conger

Moving is never what you’d call fun. When you’re dealing with a sophisticated laboratory, with all its pipettes, samples, equipment and reagents it can get downright hairy. But you won’t hear complaints from the new occupants of the Lorry I. Lokey Stem Cell Research Building.

“We’ve got boxes all over the place,” said associate professor of neurosurgery Theo Palmer, PhD, one of the first to move in. “But we’re really excited. We’re in a beautiful building with extraordinary resources. And our collaborators are close by. Now, instead of making a plan to go meet and talk with someone 20 minutes away, we’ll be bumping in to them in the hallway.”

The building’s 200,000 square feet of floor space, serving about 550 occupants, makes it the largest dedicated stem cell research building in the country, if not the world.

There should be plenty of opportunity for such instances of serendipity. The building’s 200,000 square feet of floor space, serving about 550 occupants, makes it the largest dedicated stem cell research building in the country, if not the world. But just as important, it was financed without any federal funding — buffering its occupants to some degree from the vagaries of embryonic stem cell politics.

“The Lokey Building is the first of our Stanford Institutes of Medicine and is emblematic of Stanford’s past and symbolic of our future,” said Philip Pizzo, MD, dean of the School of Medicine. “This incredible new laboratory facility is built on a design championed by faculty to facilitate research in one of the most exciting interdisciplinary areas of the 21st century — stem cell biology and regenerative medicine. It is a beacon of hope at the intersection of science and medicine, promoting discovery and innovation for the care of children and adults facing serious illness.”

“This building was designed to be a research thoroughbred,” said Chris Shay, manager of capital projects at the School of Medicine. “It’s packed with details that make other faculty members envious.” Details like the highest ratio of laboratory support space — the housing for large centrifuges, freezers, tissue culture rooms and more — to working space (about 1:1, versus about 0.3 to 1 in older research buildings in the medical school). Details like a dedicated tissue bank to store stem cell lines and animal and human tissues, a microfluidics core to collect and analyze the extremely rare cells and an in vivo imaging core to visualize stem cells in the body. Details like a state-of-the-art animal research facility with biometric entry codes, air showers and recyclable mouse cages.

“Carrying samples across campus for analysis was challenging,” said Palmer, who moved into his new digs on the first floor of the Lokey (pronounced low-kay) Building from his former laboratory in the medical school’s Lab Surge Building. “We used to have to plan our day around getting our samples where they needed to be when they needed to be there. Now some of the best resources in the world are immediately available — including extraordinary cell-sorting capabilities and some of the most advanced single-cell genetic-profiling equipment. At other places in the country these resources are essentially not available, or available only by special arrangement.”

The entire facility represents an unprecedented commitment to the promise of all types of stem cell research — from stem cells derived from embryos to induced pluripotent stem cells (or iPS cells) derived from fetal or adult tissues to cancer stem cells that give rise to tumors and cause disease relapses. Stem cell researchers have long maintained that it is critical to continue to conduct research on all types of stem cells, which have the capacity to become many types of cells and tissues, in order to move the field forward more quickly. Bringing all of these researchers under one roof will enable easy collaboration and data sharing, and together they can benefit from the advanced equipment and technical support available in the core facilities.

The ability of stem cells to renew themselves and to become various tissues holds great medical promise. The first clinical trial of human embryonic stem cells was recently launched to test the cells’ ability to regenerate spinal cord neurons in recently paralyzed patients.

“Stem cells are going to be as significant as the silicon chip that created Silicon Valley,” said philanthropist Lorry Lokey, the major benefactor for the building, with a gift of $75 million. “Stem cells are going to introduce an entirely new field of medicine for extending lives and improving the quality of life.”

In order to secure a space in the building, an investigator’s program must be on stem cells or stem-cell-related.  The building’s top level will house the Stanford Institute for Stem Cell Biology and Regenerative Medicine, formerly located off campus on Arastradero Road, while the second floor provides space for the many faculty members of the Stanford Cancer Center whose research involves stem cells. The ground floor includes neuroscience labs such as Palmer’s and the stem cell institute’sCenter for Human Embryonic Stem Cell Research and Education. Dispersed throughout the building are 60 semi-temporary "hotel" spaces for researchers from Stanford to Australia whose work would benefit from collaboration with others in the building. The basement houses the microfluidics and imaging cores, the tissue bank and the animal facilities. A tunnel connects the building with surrounding buildings and provides a route for deliveries of equipment and reagents. 

Researchers around the country and the world have taken note. One new occupant of the building, Giles Plant, PhD, was recently recruited from Perth to serve as the research director of the Stanford Partnership for Spinal Cord Injury and Repair. He and Palmer share adjoining laboratory space and common areas.

“The Lokey Building allowed us to recruit Dr. Plant,” said Palmer. Another researcher drawn by the new facility is Matthew Porteus, MD, PhD, acting associate professor of pediatrics and of cancer biology. “Part of my decision to accept Stanford’s offer was knowing that I would have space here,” said Porteus, who grew up on the Stanford campus and received his MD/PhD at the medical school. “I am thrilled to be back here and thrilled to be in the building.”

“Dallas was great,” said Porteus of his previous appointment at the University of Texas-Southwestern, but it didn’t have the stem cell expertise he needed to conduct his research into gene therapies for sickle cell anemia, hemophilia and other diseases. “Stanford is one of the few leaders in this area, and this building is all about stem cell biology.” Part of the building’s appeal, he said, is that there is a “critical mass” of people studying issues relating to stem cells. “It’s not just one plus one, but the synergy of a larger group — you get much more than you expect.”

And Porteus also pointed out another huge plus: the support services. “I’m a bit of a kid in the candy store,” he said, explaining that in his previous job, many of the techniques they used had to be learned by themselves, essentially self-taught. By contrast, he mentioned running into Cindy Klein, who runs a training center in the Lokey Building on working with human embryonic stem cells and iPS cells. “In Dallas, we had no way of getting that expertise — how you culture the cells, keep them healthy, and keep them from differentiating. But Cindy told me that any member who wants to be trained to work with these cells can do so, that’s what the center’s for. My jaw dropped.”

Robert Klein, chairman of the governing board of the California Institute for Regenerative Medicine, noted, “The Lorry I. Lokey Stem Cell Research Building at Stanford provides a world-class platform to extend the global impact of Stanford’s stem cell research on chronic disease and injury,” In May of 2008, the institute, also known as CIRM, awarded Stanford $43.6 million to build the facility as part of their "Major Facilities" grants. “The future of human suffering will surely be reduced by the research of the dedicated scientists and clinicians in this extraordinary facility,” said Klein. “While federal stem cell research funding suffers tragic, periodic setbacks and restrictions, Stanford's stem cell institute will serve as a beacon of strength and global leadership, and provide a safe harbor for the cutting edge of science.”

The dedication to research is evident on every floor of the facility, but much thought has been given to the experiences of the faculty members, postdoctoral scholars, students and staff members that will be working in the building. A wide, open central staircase leads to large landings on the second and third floor with comfortable seating areas overlooking the giant hanging sculpture by Dale Chihuly that provides a focal point for the lobby. Nearby conference rooms and break rooms on every floor offer spaces for discussion and collaboration, while common areas in the research portion of the building are equipped with flat-screen televisions and are located near administrative offices to facilitate impromptu interactions between faculty members and researchers. A lactation room with a sink and a refrigerator provides a private space for breastfeeding or pumping breast milk. 

“We tried to mix the best elements of Beckman, CCSR and the Clark Center,” said project manager Jill Knapp. Each of the building’s 33 research laboratories is situated on the outside of the building, with ceilings that slope upward toward large windows to capture natural light. Lab benches have castors, and electrical and gas and vacuum lines descend from above to allow researchers some freedom to arrange their work space, while interior, linear equipment halls offer ample support space for freezers, centrifuges and other equipment. The building’s location and exterior appearance was also carefully planned. The facility rests at one end of the Medical Promenade, which bisects CCSR and Beckman and leads to both Stanford Hospital & Clinics and Lucile Packard Children’s Hospital. Translational researchers in the building can spend their mornings in the clinic seeing patients and then walk to their labs within five minutes.

From the outside, the Lokey Building echoes aspects of buildings on Stanford’s main quad, including a red roof and limestone sides, used also in the recently-opened Li Ka Shing Center for Learning and Knowledge. “This is the second building in the medical school that uses the “kit” of design elements that we plan to incorporate into our future buildings,” said Shay. However, in contrast to the LKSC, the Lokey Building was designed to be less of a draw to the public. “The Lokey facility is almost twice as large as the LKSC,” explained Shay, “but we wanted to maintain the focus on LKSC as the center of the medical school so it was deliberately designed to invite people to enter. The Lokey Building is more inward focused.” For instance, the windows on the ground level are above the eye level of people walking by, giving researchers more privacy.

In addition to Lokey’s gift and the CIRM grant, the remainder of the building’s approximately $200 million budget was raised through private donations and university resources. Because no federal funds were used for construction, the researchers in the building can use the space for human embryonic stem cell research regardless of the research’s legal status. When President Bush banned federal funding of most human embryonic stem cell research, scientists had to be very careful about the source of the money they were using to pay both direct (for reagents and pipettes, for example) and indirect (for the space and large equipment) costs of their research. Although President Obama overturned the Bush ban on federal funding for nearly all relevant stem cell lines in 2009, another legal challenge that could reinstate the ban is currently wending its way through the courts.

The building will be dedicated on Oct. 27, but people began moving in last month. The building is expected to be fully occupied by the end of the year, which means a lot more moving stories.

“We’re sitting among mountains of unpacked boxes, looking quizzically at empty shelves,” said Palmer. “But we are all really happy to be here.”

The latest high-tech devices and services on hand in Lokey Building

The Lokey Building offers an array of state-of-the-art technology and support services easily available to researchers whose labs are in the facility. These features will help to streamline the research process, while also providing the most advanced analytical tools and supplies. Here’s a sample of these core elements:

Human embryo, oocyte, human embryonic stem cell and somatic cell bank to safely store and distribute samples for research. Previously the medical school had limited tissue and hESC banking capabilities, and demands on this off-site resource had already reached capacity.

Human embryology, human embryonic stem cell and nuclear reprogramming education core to increase the number of researchers familiar with the technologies and opportunities around embryo and embryonic stem cell research. Classes will be hosted within the building to provide hands-on laboratory experience in the growth, derivation, differentiation, analysis and reprogramming of human embryonic stem cells.

Microfluidics laboratory to analyze the genetic, epigenetic and proteomic profiles of single cells. This capability is necessary to allow researchers to study individual, very rare stem cells, without requiring large, pooled samples. The core is unique worldwide and uses technology invented at Stanford by Stephen Quake.

Flow cytometry core housing eight state-of-the-art, multi-color cell sorters and/or analyzers, technology that was invented at Stanford. Cell sorting is necessary for the rapid and accurate characterization of populations of cells and to isolate rare subpopulations, such as cancer stem cells, for research. This core augments services currently provided by the Stanford Shared FACS Facility.

Cancer tissue bank and rapid autopsy/tissue core to store surgical samples of primary and metastatic cancers and normal tissues. A ready source of live cells will facilitate research on adult tissue and cancer stem cells. 

Advanced in vivo imaging will allow the visualization of tissue and stem cell niche architecture at near-ultrastructural resolution and of normal, abnormal and transplanted stem cells within a living animal. The core will rely on emerging technologies that are not yet represented on campus, including array tomography, in vivo confocal microscopy, micro-PET and small animal ultrasound.

Behavioral and Functional Neuroscience Laboratory to translate the findings of stem cell research through functional cognitive, psychiatric, sensory and motor function, physiology and toxicology testing in rodents. The service will include experimental rodent models of neurodegenerative, neurological, and psychiatric disorders for the preclinical assessment of stem cell therapies.