Spotlight on

Dr. Timothy Veenstra
Director, Biomedical Proteomics Program
NCI/SAIC Research Technology Program

Spotlight Archive

Mass spectrometry (MS) is fast becoming the leading tool for rapid and accurate identification of proteins that play a key role in the development of cancer. Dr. Timothy Veenstra, Director of the Mass Spectrometry Center, Biomedical Proteomics Program (BPP), has recognized the potential power of this technique in detecting early-stage cancer.

The mission of the NCI-Proteomics Program is to identify and characterize the protein signatures of human cancer cells and tissues and to apply proteomic technologies directly to patient diagnosis, toxicity monitoring and therapeutic interventions. To accomplish its mission, the program conducts both biomedical and clinical proteomics studies. Dr. Veenstra heads the BPP, part of the NCI/SAIC-Frederick, Inc. Research Technology Program (RTP). Dr. Lance Liotta of the NCI's Center for Cancer Research (CCR), and Dr. Emanuel Petricoin of the Food and Drug Administration co-direct the Clinical Proteomics Program (CPP). Many laboratories contribute to the biomedical component:   the Laboratory of Proteomics and Analytical Technology, directed by Dr. Veenstra; the Laboratory of Molecular Technology, directed by Dr. David Monroe; the Protein Chemistry Laboratory, directed by Dr. Robert Fisher; the Protein Expression Laboratory, directed by Dr. James Hartley; and the Advanced Biomedical Computing Center, directed by Dr. Stan Burt. These five laboratories form the core of the BPP.

Although much of the actual research is performed within his own lab, Dr. Veenstra does rely heavily on the other BPP laboratories for intellectual input. All of the labs meet bi-weekly to update each other and to discuss potential new collaborations. They must first decide whether a project is feasible using the current technology. Another consideration is whether the project would further the field or our understanding of cancer.

A New Diagnostic Tool?

The BPP has set several goals based on current discoveries.   One goal is to take the proteomic pattern diagnostic tool they helped to develop and refine it so that it can be used in a clinical setting; meaning that 5 to 10 years from now this tool may be the standard for detecting early-stage cancer. "We see that the big success would be someday that this [tool] could be used in a clinical setting and would ultimately save lives. That would be just great," says Dr. Veenstra.   Another goal is to make the proteomic pattern test simpler. Many of the BPP's projects revolve around global analysis of cells. This process compares the cells-of-interest to other cell types or to cells that have been treated with a drug (or some other agent) in order to find differences among the proteins of the two different cell types.   "What our technology allows people to do is to get a broad survey of the cell in a pretty rapid fashion and hopefully discover things that they couldn't if they took a systematic approach where they said 'let's see what happens to this protein' and they look at each protein in an individual experiment. Doing that means that you are looking at 2 or 3 days for each protein. So you can imagine in a year with 200 or so working days a year, you could get through 100 proteins, if you are ultra-efficient. Now we can get through about 1,400 proteins in a matter of 3 weeks," states Dr. Veenstra.

Dr. Veenstra's group also conducts targeted proteomics studies for investigators who have already identified a protein-of-interest and want to use this protein as a building block to find other interacting proteins. If a lab can develop a way to isolate the protein-of-interest, along with other proteins that it binds to, the BPP can then help identify those proteins.   In addition, the BPP develops assays for specific molecules in serum, plasma, or urine to measure the amount of protein in these fluids. After developing the assay, Dr. Veenstra's group will translate it into a highly automated procedure in which hundreds of samples can be analyzed within a week.   Currently, the BPP is working not only with ovarian cancer but also with lung, prostate, pancreatic and breast cancer.   Dr. Veenstra and his colleagues hope that the proteomics pattern tool will be able to detect these other types of cancer at an early stage, too.

Mass Spectrometry: How Does It Work?

MS works much like a bathroom scale. "We refer to it sometimes in the lab as an expensive bathroom scale," says Dr. Veenstra.   He further explains that spectrometry is a tool that measures something and what his group is trying to measure is mass.   MS measures not only the mass as a whole but can also be used to fragment a molecule, breaking it into pieces and then measure the masses of those individual pieces. "Now this information is actually very powerful in identifying any molecule uniquely," says Dr. Veenstra.   "If you took a spider and an insect and you measured the masses of each, you are not going to be able to tell whether it is a spider or an insect, but if you are able to break it into components and say, 'I measured 8 legs here and 6 legs over here,' then you could tell if it were a spider or an insect," he explains.   Measuring the fragments gives you a good indication of what the molecule actually is.   "It [MS] simply measures the mass but the mass is actually a very powerful parameter to determine what a molecule is," explains Dr. Veenstra.

MS has many benefits. It is fast, sensitive, accurate, and automated. "For example, we can, in a single day, identify hundreds if not thousands of different species," Dr. Veenstra states. "You can run samples back-to-back unattended. You can run it 24/7," he adds.   The level of sensitivity provided by MS offers scientists the ability to measure incredibly small amounts of material with absolutely no ambiguity.   "We know exactly what the compound is when we do identify it," says Dr. Veenstra.

However, there are downfalls to this procedure when using it to try to diagnose cancer. One of the biggest right now is that scientists don't understand what they are actually "seeing" within the proteomic patterns. The main focus in proteomic pattern diagnostics is not on the identification of the peaks since the value of identifying them is not clear at this stage.   "To me, that is the biggest disadvantage in this area: we don't at this point fully understand what we are seeing because we haven't gone into identifying what those peaks are," he cautions.

An Early Interest in Science

Dr. Veenstra has always been interested in science. "I've probably been interested in science ever since I can remember; even when I was 5 and 6 years old I can remember having an interest in science. I initially wanted to be a medical doctor but as I got older and I realized how long it takes to study to be a medical doctor and then my impatience kind of overruled that," says Dr. Veenstra.  

As he grew up, Dr. Veenstra set his sights on either the construction industry or becoming a scientist. "As I got a little bit older, I got into the construction industry and I enjoyed that a lot and almost made a decision to go into construction instead of science. But the one thing I like about science is the climate-controlled building, makes your job much easier," he explains.

Dr. Veenstra obtained his bachelor's degree in chemistry from Trent University, Peterborough, Ontario, Canada, and his PhD in biochemistry from the University of Windsor, also in Ontario. While completing his post-doctoral training at the Mayo Clinic Foundation, Dr. Veenstra gained experience in molecular and cell biology, which is where he got his first look at the wonders of MS as a bioanalytical tool. During one project he and his colleagues were trying to determine calcium binding to a protein. "We came across a paper where someone had done it using MS, which was kind of foreign to me at the time, but we tried it and got very successful results," Dr. Veenstra said. "That's where I really got my first taste and introduction to proteomics and MS," he adds. After his post-doctoral training, Dr. Veenstra worked as a staff scientist at Pacific Northwest National Laboratories (PNNL).   He became Director of the RTP's Mass Spectrometry Center in September of 2001.

Dr. Veenstra advises young scientists to pay attention in English and writing classes. "To be a successful scientist, you need to be able to communicate your results effectively," Dr. Veenstra said. He also wants young scientists to make sure that their science doesn't become their life. "There is enough time in a standard work week to become a great scientist," Dr. Veenstra said, "Make sure you spend enough time with your family and friends doing other things."  

The one thing that Dr. Veenstra wants the general public to know about his research is that it is geared toward identifying those characteristics of a protein or cell system that cannot be found using conventional protein characterization methods. A cell has at its disposal 35,000 genes and screening every protein product individually within that cell would be impossible. "Our research allows many of these proteins to be analyzed in a rapid fashion; however, the relevance of key proteins found during this discovery process still needs to be ascertained on the individual protein level," adds Dr. Veenstra.

Written by Kathryn Ellis
Office of Communication
Center for Cancer Research (CCR)
National Cancer Institute at Frederick

Edited by:
Sue Fox, Office of Communication, CCR
Maritta Grau, Scientific Publications, Graphics and Media
SAIC-Frederick, Inc.

Photography by Martha Welch
Scientific Publications, Graphics and Media
SAIC-Frederick, Inc.

Web Graphics and Development by Jim Miller
Computer and Statistical Services
National Cancer Institute at Frederick