Skip to Page Level NavigationSkip to Page ContentSkip to Page Contact Information
Paul Harding (right), associate professor of biology, speaks to Sean Taylor (center), doctoral student, while undergraduate students Michael Markesbery and Katie Johnson work in the lab.
Paul Harding (right), associate professor of biology, speaks to Sean Taylor (center), doctoral student, while undergraduate students Michael Markesbery and Katie Johnson work in the lab. Photo: Scott Kissell
Share on Facebook Share on Twitter Print this Page

Miami professor, former grad student earn patent for cell conversion process

The difference between white and brown fat

Fat cells have different functions.

White fat is the kind of fat that's common in the abdomen area of adults. It helps insulate the person and protect their internal organs. "It’s a good long-term energy source," Paul Harding said.

Brown fat is abundant in human babies and hibernating animals. People who live in very cold climates, such as Eskimos, have a little more brown fat than people living here in Ohio.

"As we get to be adults, we lose the majority of that brown fat except in certain areas. We have some around our shoulders and some around our aorta by our heart. Its function is to generate heat," Harding said.

Brown fat contains a lot of mitochrondria, the energy producers in animal and plant cells. Brown fat uncouples that energy process and "puts everything through what’s called an uncoupling protein to make heat instead of energy," he said.

This is the final story in a three-part series on patents at Miami.  (Read part one and part two online at Miami News.)

Imagine if scientists could find a way to convert any type of cells into energy-burning brown fat cells that could metabolize blood sugar to generate heat.

Better yet, what if they could reprogram a cancerous tumor into those brown fat cells?

Paul Harding, associate professor of biology at Miami University, is investigating whether both scenarios might be possible in an animal.

If it works, Harding said, the breakthrough could have potential implications in the battles against obesity, diabetes and cancer.

"We've converted cancer cells in a dish into brown fat, so logically I think we can probably do it in an animal, too. We'll see. You don't know until you try," he said, cautioning the research is still preliminary.

Harding and former graduate student Zhenqing Zhou (Miami PhD '09) received approval on June 4 to patent the process, "Cell Transdifferentiation into Brown Adipocytes." That’s the conversion of any type of cell into brown fat in a culture dish.

This is Harding's third patent, his first at Miami. The research findings will be published in the December issue of the journal, Growth Factors.

The study authors are Zhou, Maureen Darwal (Miami '08), Esther Cheng (Miami '10), doctoral student Sean Taylor, Erning Duan (MS Miami '10) and Harding.  

Harding credits Darwal, who worked in his lab as an undergraduate zoology major, for laying the foundation for this area of fat research and "changing the whole focus of our lab."

Prior to that, the focus was on determining which part or parts of the growth factor were involved in making cells grow and divide.

Darwal wanted to make a model for cancer so she put the growth factor Heparin-binding epidermal growth factor (HB-EGF) and gene ADAM12, an enzyme that acts upon HB-EGF, together in cells.

"I'm sure everyone would expect those cells to grow and divide very rapidly, but they didn't," Harding said. "They turned to fat."

Harding thought Darwal made an error so he had her re-run the experiment. The findings came back the same.

Conversion of cancer cells into brown fat.

These images demonstrate the successful conversion of cancer cells into brown fat in a culture dish after the cancer cells were combined with two genes, Heparin-binding epidermal growth factor (HB-EGF) and ADAM12, an enzyme that acts upon HB-EGF. Photo provided by Paul Harding.

"I was absolutely shocked," said Harding, who didn't see the spindle-shaped cells he expected. Instead, the cells were round and contained obvious fat.

"These serendipitous findings are sometimes very, very fruitful," he said.

Harding directed Zhou to determine what type of fat it was.

"Zhenqing did a fantastic job of identifying that it is brown fat," Harding said of Zhou, now a post-doctoral fellow at Washington University in St. Louis.

Darwal — who graduated from Lake Erie College of Osteopathic Medicine in June and is now doing a neurosurgery residency at Hackensack University and Saint Barnabas medical centers in New Jersey — said she's ecstatic the research is being recognized in Growth Factors.

The initial discovery of adipose (fat) tissue was "extremely intriguing," Darwal said. "It was incredible to think that our research may be able to change someone's life in the future."

Potential implications

Miami researchers are now trying to determine the functionality of the reprogrammed cells, which can produce glucose when stimulated.

"In theory, they should suck up glucose like it's going out of style," Harding said. "With that being said, we think there are tremendous therapeutic capabilities for Type 2 diabetes."  The chronic condition affects the way a body metabolizes sugar, the main source of fuel.

The Centers for Disease Control and Prevention has called obesity a national epidemic and a major contributor to some of the leading causes of death, including heart disease, stroke, diabetes and some types of cancer.
 
Although targeting diabetes is one of Harding's hopes, the patented process actually is directed toward tumors, he said.

"We want to convert a tumor to brown fat," he said, noting they would study mice infected with tumors and placed in cold chambers to see if the tumors turn to fat.

Harding noted a possible downside: The viruses would also infect other tissues, such as the heart and liver.  "Somebody else would need to assist us in how to target viruses to specific cells," he said.

Harding's third patent a charm for Miami

Paul Harding

Paul Harding

Harding's two other patents stem from postdoctoral research done with a colleague at the Ohio State University. Both relate to connective tissue growth factor (CTGF). It plays an important role in many biological processes, but is critical in fibrotic disease such as lung and liver fibrosis, and various forms of cancer.

Harding conducted postdoctoral research at Children's Hospital in Columbus and at Ohio State before joining the biology department at Miami in 2001.

"When I was at Ohio State, I helped identify the most potent form that has been identified," he said. FibroGen, Inc., a research-based biotechnology company, purchased the rights to the patent Harding has with the researcher and hopes to develop it into a drug.

Harding strongly believes in involving undergraduate students in his research projects.

"I think it's all about grabbing these students when they are young, when they're in their freshmen and sophomore years," he said.

Darwal said her research experience had a lasting impact on her.

"Dr. Harding took me under his wing my freshman year with such enthusiastic guidance that it truly sparked my intellectual curiosity for the career path I ultimately took," she said.

Now other Miami undergraduate students are getting that same opportunity. Michael Markesbery, a junior zoology major from Cincinnati, and Katie Johnson, a junior biology major from Chillicothe, are working with Harding and Taylor on this brown fat research.

"It's incredible. If someone would have asked me coming out of high school if I would be doing this by junior year in college, I would have said there's no way," Markesbery said.

Markesbery will help present findings at the American Society for Cell Biology conference in New Orleans in December.

For Taylor of Middletown, the research will be a key part in working toward his doctorate in Miami's cell molecular structural biology program.

"Cancers are invasive cells that divide uncontrollably. We've found a way to make cells change what they are, and stop dividing," he said.

Taylor knows "a lot of things that work in dishes don't come to fruition in animals," but he's anxious to investigate that next step to determine if it might be possible.

Grant funding

Harding's research was supported by grant funding from the National Institutes of Health from 2009 through 2012. He recently applied for another NIH grant to continue the research.

He hopes the patent will help secure that funding, but also hopes to eventually draw attention from pharmaceutical companies.

While Harding is concerned about government research funding becoming more limited in recent years due to budget cuts, he thinks it can't hurt that this research could have potential implications with diabetes and cancer.

"Those are big areas in health today," he said, "so there should be a lot of interest."

Written by Margo Kissell, university news and communications, kisselm@miamioh.edu
     

University Communications and Marketing

University News and Communications
17 MacMillan Hall
Miami University
Oxford, OH 45056
513-529-7592
513-529-3257 (fax)

The difference between white and brown fat

Fat cells have different functions.

White fat is the kind of fat that's common in the abdomen area of adults. It helps insulate the person and protect their internal organs. "It’s a good long-term energy source," Paul Harding said.

Brown fat is abundant in human babies and hibernating animals. People who live in very cold climates, such as Eskimos, have a little more brown fat than people living here in Ohio.

"As we get to be adults, we lose the majority of that brown fat except in certain areas. We have some around our shoulders and some around our aorta by our heart. Its function is to generate heat," Harding said.

Brown fat contains a lot of mitochrondria, the energy producers in animal and plant cells. Brown fat uncouples that energy process and "puts everything through what’s called an uncoupling protein to make heat instead of energy," he said.

Locations
Luxembourg
West Chester
Middletown
Hamilton
Oxford
  • Luxembourg
    Luxembourg

    John E. Dolibois European Center, Luxembourg

    One of Miami's oldest continuous study abroad programs, the Miami University John E. Dolibois Center (MUDEC) in Luxembourg offers students the opportunity to enroll in Miami classes taught by European-based and Ohio-based Miami faculty. Students enjoy a unique combination of first-class academics, engagement in the local community, and various faculty-guided and independent travel opportunities.

    Contact and emergency information for the Luxembourg Campus. Starting with general contact info on the left; additional contact and emergency information on the right.

    Château de Differdange
    1, Impasse du Château
    L-4524 Differdange
    Grand Duchy of Luxembourg
    luxembourg@MiamiOH.edu
    MiamiOH.edu/luxembourg

    217-222 MacMillan Hall
    531 E. Spring Street
    Oxford, Ohio 45056, USA

    Directions

    Main Operator: 011-352-582222-1
    Oxford-based Coordinator: 513-529-5050
    Emergency info: MiamiOH.edu/emergency

  • West Chester
    West Chester

    Voice of America Learning Center

    Located midway between Cincinnati and Dayton along I-75, the Voice of America Learning Center (VOALC) offers undergraduate and graduate courses and programs drawn from Miami's Regional and Oxford campuses. Home to Miami's MBA program, the Learning Center provides ready access to graduate programs for area educators and courses leading to the BIS degree for undergraduates.

    Contact and emergency information for the Voice of America Campus. Starting with general contact info on the left; additional contact and emergency information on the right.

    7847 VOA Park Dr.
    (Corner of VOA Park Dr. and Cox Rd.)
    West Chester, OH 45069
     
    voalc@MiamiOH.edu
    MiamiOH.edu/voalc

    Printable Floor Plan
    Directions

    Main Operator: 513-895-8862
    (From Middletown) 513-217-8862
    Emergency info: regionals.MiamiOH.edu/emergency

  • Middletown
    Middletown

    Middletown Regional Campus

    Nestled on 141 acres near I-75, Miami University Middletown offers bachelor's degrees, associate degrees, and beginning coursework for most four-year degrees. Nearby Greentree Health Science Academy immerses Miami's nursing and health information technology students in the health care experience while taking classes.

    Contact and emergency information for the Middletown Campus. Starting with general contact info on the left; additional contact and emergency information on the right.

     4200 N. University Blvd.
    Middletown, OH 45042
    regionalwebmaster@MiamiOH.edu
    regionals.MiamiOH.edu

    Printable Campus Map
    Directions

    Main Operator: 513-727-3200
    (Toll-free) 1-86-MIAMI-MID
    Office of Admission: 513-727-3216
    Campus Status Line: 513-727-3477
    Emergency info: regionals.MiamiOH.edu/emergency

  • Hamilton
    Hamilton

    Hamilton Regional Campus

    A compact, friendly, commuter campus, Miami Hamilton offers bachelor's degrees, associate degrees, and beginning coursework for most four-year degrees. Small class sizes, on-site child care, and flexible scheduling make Miami Hamilton attractive to students at all stages of life and career.

    Contact and emergency information for the Hamilton Campus. Starting with general contact info on the left; additional contact and emergency information on the right.

    1601 University Blvd.
    Hamilton, OH 45011
    regionalwebmaster@MiamiOH.edu
    regionals.MiamiOH.edu

    Printable Campus Map
    Directions

    Main Operator: 513-785-3000
    Office of Admission: 513-785-3111
    Campus Status Line: 513-785-3077
    Emergency info: regionals.MiamiOH.edu/emergency

  • Oxford
    Oxford

    Miami University, Oxford Ohio

    Nationally recognized as one of the most outstanding undergraduate institutions, Miami University is a public university located in Oxford, Ohio. With a student body of 16,000, Miami effectively combines a wide range of strong academic programs with faculty who love to teach and the personal attention ordinarily found only at much smaller institutions.

    Contact and emergency information for the Oxford Campus. Starting with general contact info on the left; additional contact and emergency information on the right.

    501 E. High St.
    Oxford, OH 45056

    Printable Campus Map
    Directions

    Main Operator: 513-529-1809
    Office of Admission: 513-529-2531
    Vine Hotline: 513-529-6400
    Emergency info: MiamiOH.edu/emergency