UCSF

Zev Gartner receives NIH New Innovator Award to build complex human breast tissue

Zev Gartner, PhD, has been named a recipient of the 2013 National Institutes of Health (NIH) Director’s New Innovator Award, which will provide his lab with up to $1.5 million in research funding over the next five years.

Gartner, a faculty member in the UCSF School of Pharmacy’s Department of Pharmaceutical Chemistry will use the funding to develop a revolutionary new way to rapidly and precisely build 3–D human tissue in vitro—among the most structurally complex and detailed to date—for studying basic biology and testing therapeutics.

Specifically, Gartner plans to build a functional human mammary gland, starting with modular substructures such as the lining of the milk ducts, made of two cell types in layers, and working up a hierarchy of complexity incorporating the ducts with blood vessels, immune cells, and connective tissue. These models will provide new insight into how normal human tissues assemble themselves during development, and conversely, how they break down in diseases such as breast cancer.

This marks the fourth year in a row that a young School faculty member has won this highly selectively funding, designed “to support exceptionally creative new investigators who propose highly innovative research projects that have the potential for unusually high impact.” This year it was awarded to 41 scientists nationwide.

Building tissues from healthy, diseased breast cells

Collaborating with the lab of Mark LaBarge, PhD, staff scientist at Lawrence Berkeley National Laboratory, Gartner will use healthy cells cultured from breast reduction surgeries and, for certain studies, their malignant derivatives, to create structures controlled down to the positioning of individual cells.

“These cells allow us to build a tissue step-by-step,” says Gartner. “But we aim to apply the method toward asking questions about how human tissues build themselves.”

The synthesized models will enable studies of how cellular heterogeneity, injury, and/or disturbances in the relay of signals among different cell types, contribute to breast cancers. The tissues could also be used to test and develop new diagnostic methods and therapies, and more broadly to prototype new tissue engineering strategies.

Rapid prototypes to study human cells in natural contexts

The Gartner lab project addresses a key unmet need in biomedical research for an improved way to study the function of communities of interacting cells working together, known as tissues, that:

  • uses human cells rather than an animal model, as the ubiquitous mouse models can fail to recapitulate many aspects of human physiology.
  • precisely controls which cell types interact and the spatial arrangement of groups of cells for experimental alteration and analysis.
  • are grown in three-dimensional extra-cellular matrices, as they naturally exist in our bodies, rather than in flat culture dishes.
  • are generated via rapid (one day from concept to constructed tissue) and inexpensive prototyping techniques that can incorporate multiple cell types.

“The big picture is to put together a rapid prototyping tool for building multicomponent 3-D tissues, and one that has the ability to put a specific cell in precisely the right location and context of the larger tissue,” says Gartner.

Total synthesis of tissues instead of molecules

Gartner analogizes this new approach to tissue building—and the potential lessons to be learned—to the long-established process in organic chemistry known as total synthesis in which complex biologically active molecules are built from more basic chemical building blocks.

The creation of physically similar but slightly altered molecules (structural analogs) has helped reveal how the structure of molecules affects function, for example as drugs. The process of total synthesis therefore reveals new chemical principles and has led to the discovery of life-saving pharmaceuticals.

Using specific cell types to construct tissues, rather than chemical compounds to make molecules, should likewise yield new, key insights into tissue organization and cellular interactions.

In 2012 and 2011 the New Innovator award went to Gartner’s department colleagues, Xiaokun Shu, PhD, and Bo Huang, PhD, respectively. In 2010, the five-year NIH funding award went to Michael Fischbach, PhD, a faculty member in the Department of Bioengineering and Therapeutic Sciences, a joint department of the UCSF Schools of Pharmacy and Medicine.


About the School: The UCSF School of Pharmacy is a premier graduate-level academic organization dedicated to improving health through precise therapeutics. It succeeds through innovative research, by educating PharmD health professional and PhD science students, and by caring for the therapeutics needs of patients while exploring innovative new models of patient care. The School was founded in 1872 as the first pharmacy school in the American West. It is an integral part of UC San Francisco, a leading university dedicated to promoting health worldwide.