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Creative Minds: Engineering Targeted Breast Cancer Treatments

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Photo of Debra Auguste

Debra Auguste

A few years ago, Debra Auguste, a chemical engineer then at Harvard University, was examining the statistics on breast cancer: the second most common cancer in women in the U.S. after lung cancer. She was disturbed to discover that of all the ethnic groups, African American women with breast cancer suffered the highest mortality rates—with 30.8% dying from the disease [1-3].

As an African American woman, Auguste was stunned by this correlation. She wondered whether there was some genetic aspect of breast cancer cells in African Americans that made these cancers more aggressive and more difficult to cure.

Creative Minds: Mapping Molecules in their Cellular Compartments

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Alice Ting

Alice Ting, Ph.D.
Credit: Vilcek Foundation

If you were trying to understand how a city functions, it would be useful to map not only its streets and buildings, but to identify all of the people in the city and pinpoint their locations at different times throughout the day. That’s pretty much what biologists would like to do for a cell: map an entire living cell in a way that identifies all of its parts and shows their precise locations at various points in time.

The challenge has been developing the tools and technologies needed to create such a map. Among those who have risen to that challenge is Alice Ting, an associate professor at the Massachusetts Institute of Technology (MIT), Cambridge, MA, and winner of a 2008 NIH Director’s Pioneer Award and a 2013 NIH Director’s Transformative Research Award.

DNA Barcodes Interrogate Cancer Cells

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Blue and green blobs with one purple and red blob with a yellow and red striped box

Caption: A mix of cells collected from an abdominal cancer. The cancer cells (green) are positive for a cell surface cancer marker called EpCAM. The red cell is a normal mesothelial cell. The nuclei of all the cells are stained blue. Each of the five rows in the red, orange, and yellow “heat map” in the corner represents one cell, and the intensity of the color in each of the ~30 narrow columns reflects the abundance of a particular protein. It is apparent that there is a lot of heterogeneity in this collection of cancer cells.
Credit: Ralph Weissleder, Center for Systems Biology, Massachusetts General Hospital, Boston

The proteins speckling the surface of a cancer cell reveal critical clues—the type of cancer cell and a menu of possible mutations that may have triggered the malignancy.  Since these proteins are exposed on the outside of the cell, they are also ideal targets for so-called precision cancer therapies (especially monoclonal antibodies), optimized for the particular individual. But in the past, to analyze and identify these different proteins, large samples of tissue have been needed. Typically, these are derived from surgical biopsies. But biopsies are expensive and invasive. Furthermore, they aren’t a practical option if you want to monitor the effects of a drug in a patient closely over time.

Using a minimally invasive method of cell sampling called fine needle aspiration, physicians can collect miniscule cell samples frequently, cheaply, and safely. But, until now, these tiny samples only provided enough material to analyze a handful of cell surface proteins. So, it comes as particularly good news that NIH-funded researchers at Massachusetts General Hospital in Boston have developed a new technology that quickly identifies hundreds of these proteins simultaneously, using just a few of the patient’s cells [1]. The key to this new method is a clever adaptation of the familiar barcode.

Snapshots of Life: Amyloid Glows in Polarized Light

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Amyloidosis as seen under a microscope

Credit: William Lewis, Emory University School of Medicine, Atlanta

While this may look like one of those bold canvases from the brush of an Abstract Expressionist, it’s actually a close-up of the biology underlying a rare, but relentless, group of conditions known as amyloidosis. This winner of the Federation of American Societies for Experimental Biology’s 2013 BioArt contest traces in exquisite detail the damage that amyloid, which is the abnormal accumulation of specific extracellular proteins, can inflict on the heart.

Fighting Obesity: New Hopes From Brown Fat

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Artist rendition of a xray showing brown fat as glowing green

Caption: Brown fat—actually marked in green on this image—is wrapped around the neck and shoulders. This “shawl” of brown fat warms blood before it travels to the brain.
Illustration: John MacNeill, based on patient imaging software designed by Ilan Tal. Copyright 2011 Joslin Diabetes Center

If you want to lose weight, then you actually want more fat, not less. But you need the right kind: brown fat. This special type of fatty tissue burns calories, puts out heat like a furnace, and helps to keep you trim. White fat, on the other hand, stores extra calories and makes you, well, fat. Wouldn’t it be nice if we could instruct our bodies to make more brown fat, and less white fat? Well, NIH-funded researchers have just taken another step in that direction [1].

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