Scientist Profile - Carlos Barbas

Scripps Research Professor Carlos Barbas has been involved in developing numerous technologies over the past several years that have resulted in several drugs currently in clinical trials to combat disease.

Carlos and his colleague Scripps Research President Richard A. Lerner developed a new class of drugs in 2002.  Their work offers a groundbreaking way to physically combine antibodies, which are large, soluble molecules that remain in the body for long periods of time, with small molecule drugs and peptides, which can kill disease-causing cells, but may be expelled from the body too quickly to be effective as a therapy.  These hybrid molecules, called “chemically programmed antibodies,” have the desired properties of each – killing disease-causing cells and staying in circulation long enough to dramatically enhance the drug’s effectiveness. 

Empowered by these compelling results, Carlos and Dr. Lerner founded CovX, a biotechnology venture, which was later acquired by Pfizer to develop this unique and powerful class of antibodies.

The approach has led to a number of compounds under development against cancer, HIV-1, and metabolic disease.  Carlos and his colleagues found that the hybrid molecules they developed had a profound effect on the size of tumors in mouse models, shrinking tumors of melanoma, breast, and colon cancer.

“We were able to show the chemically programmed complex had at least 1,000-fold increase in the therapeutic effect compared with the small molecule alone,” said Carlos.  “With that came the idea that this was too powerful an approach not to push into human studies.”

Today, three of the hybrid compounds developed by CovX have completed preclinical work with promising results as anti-tumor agents and are progressing in clinical trials.   A fourth compound to treat diabetes is also in clinical trials.  Numerous other drugs based on this intriguing technology are in early phases of development at CovX/Pfizer.  This technology represents the first time catalytic antibodies have been used in human therapy.

“It’s very rare that an entirely new class of drugs is developed that can be applied in so many therapeutic areas,” said Carlos.  “It has been a dream of mine as a scientist to develop drugs that make a difference.  I couldn’t be more excited by these developments.  I’ve envisioned a cure for a disease since I was a child, and getting closer to this realization really drives me.”

The work was made possible by the generous philanthropy of the Skaggs family, whose milestone gift opened and sustained the Skaggs Institute of Chemical Biology at Scripps Research.  “Only through funding from the Skaggs Institute could such high-risk, high-reward studies be pursued in today’s funding environment – this work is often too speculative to be funded initially by the National Institutes of Health” said Carlos.

A second focus of his laboratory also involves the development of new immunotherapeutic approaches to disease.  To accomplish this, his group developed phage display methods for the selection and in vitro evolution of antibodies.  Carlos and his colleagues applied these to viral diseases and their current efforts focus on creating new genetic and chemical approaches to immunotherapy that include developing novel chemotherapeutics, small molecules that function in concert with antibodies, and gene therapy approaches that use intracellular antibodies.  Carlos and his colleagues are applying these methods to create effective therapies for breast and ovarian cancer, melanoma, and AIDS.  The phage display and synthetic antibody methodologies developed by Carlos and his colleagues are now being used broadly by a number of pharmaceutical firms, who have developed numerous drugs or improved existing drugs using the methodology.

A third focus of the lab is the design, optimization, and utilization of transcription factors for the directed regulation of gene expression.  To accomplish this, Carlos and his colleagues have developed zinc finger protein based transcription factors as a robust technology for endogenous gene regulation.  They are applying this approach to provide transcription-based solutions to disease, and have licensed the technology to Sangamo Biosciences who currently have a drug in clinical trials for ALS (or Lou Gehrig’s Disease).  Other far-reaching studies involving zinc finger proteins involve developing new approaches in stem cell therapies that will allow scientists to specifically and safely insert or correct genes.

Carlos started with Scripps Research as a postdoctoral fellow in 1990, after receiving his Ph.D. from Texas A&M University, and has been thriving here ever since.

“This is the place where I could do the research I wanted to do.  Richard Lerner became my mentor and instilled in me his drive for fearless exploration of diverse areas of science and medicine,” said Carlos.

“At Scripps Research, you’re free and encouraged to explore your scientific passion without boundaries and departmental constraints,” Carlos continued.  “You’re not pigeonholed as a chemist or a biologist – it’s the feature I most like about Scripps Research.”

Carlos’s work is so promising that it’s turning some important heads.  He was recently named a winner of the National Institutes of Health (NIH) Director’s Pioneer Award.  He was selected for the award on the basis of his proposal for future bold and high-impact work.  Specifically, his proposal concerns chemically programming immunity, research that could lead to “instant immunity” vaccines for the flu, HIV-1, and cancer.  The new approach would overcome a major drawback of current vaccinations – the lag time of days, or even weeks, that it normally takes for immunity to build against pathogens such as bacteria and viruses.

“NIH is pleased to be supporting scientists from across the country who are taking considered risks in a wide range of areas in order to accelerate research,” said NIH Director Francis Collins.

“This is a tremendous recognition that Carlos is doing outstanding work,” said Peter Wright, chair of the Scripps Research Department of Molecular Biology.  “His laboratory continues to tackle some extremely important scientific questions that lay the foundations for future therapeutics and vaccines.”

Carlos also received the Tetrahedron Young Investigator Award, Bioorganic & Medicinal Chemistry, for 2009.  The award is presented to individuals under the age of 45 who have exhibited “exceptional creativity and dedication” in their fields.

In another testament to his work, according to ISI Essential Science Indicators, a web-based data file reflecting scientific papers published in the last decade, Carlos ranks in the top one percent in terms of total citations in the fields of chemistry, microbiology, and biology and biochemistry.  His productivity and impact have earned him an h-index of 77 and 50 issued U.S. patents.  His latest inventions are behind his founding of his third biotechnology company, Zyngenia, that aims to create ever more powerful drugs for cancer and inflammation.

Carlos was nurtured into science by his mother and he is leaving that same imprint on his own children.  “I grew up in an era when men were first walking on the moon and science was the big thing.  For as long as I can remember, I wanted to be a scientist, a brain surgeon, or an astronaut … and my mom was more than happy to instill these pursuits in my mind,” quipped Carlos.  “I would be pleased to pass on the torch to my son and daughter, who are in college and high school.  They both have an interest in science and participated in the Scripps Research summer student internship program this summer,” said a proud father.