Nancy A. Thornberry is the founding

CEO A chief executive officer (CEO), also known as a central executive officer (CEO), chief administrator officer (CAO) or just chief executive (CE), is one of a number of corporate executives charged with the management of an organization especially ...

and current Chair, R&D at Kallyope Inc. in New York City. She previously worked with Merck Research Laboratories (MRL), joining the company in 1979 as a biochemist and retiring from the position of Senior Vice President and Franchise Head, Diabetes and Endocrinology in 2013. In 1992, Thornberry identified the first

caspase Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cystei ...

, Caspase-1/Interleukin-1 converting enzyme (ICE). In 1999, Thornberry initiated Merck's research into

dipeptidyl peptidase-4 Dipeptidyl peptidase-4 (DPP4), also known as adenosine deaminase complexing protein 2 or CD26 (cluster of differentiation 26) is a protein that, in humans, is encoded by the ''DPP4'' gene. DPP4 is related to FAP, DPP8, and DPP9. The enzyme was d ...

, leading to the development of FDA-approved treatments for

Type 2 diabetes Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, ...

. She has received a number of awards, including the 2011 PhRMA Discoverer’s Award.

Education

Thornberry grew up in

South Bend, Indiana South Bend is a city in and the county seat of St. Joseph County, Indiana, St. Joseph County, Indiana, on the St. Joseph River (Lake Michigan), St. Joseph River near its southernmost bend, from which it derives its name. As of the 2020 United S ...

. As of 1979, she earned a B.Sc. in Natural Science from

Muhlenberg College Muhlenberg College is a private liberal arts college in Allentown, Pennsylvania. Founded in 1848, Muhlenberg College is affiliated with the Evangelical Lutheran Church in America and is named for Henry Muhlenberg, the German patriarch of Luthera ...

Allentown, Pennsylvania Allentown (Pennsylvania Dutch language, Pennsylvania Dutch: ''Allenschteddel'', ''Allenschtadt'', or ''Ellsdaun'') is a city in Lehigh County, Pennsylvania, Lehigh County, Pennsylvania. The city has a population of 125,845 as of the 2020 United ...

Career

Thornberry joined Merck Research Laboratories (MRL) in

Rahway, New Jersey Rahway () is a city in southern Union County, in the U.S. state of New Jersey. A bedroom community of New York City, it is centrally located in the Rahway Valley region, in the New York metropolitan area. The city is southwest of Manhattan ...

as a biochemist in 1979. In 1999 she was appointed the Director of Enzymology, and in 2001 the Director of Metabolic Disorders, with further promotions in 2007, 2009 and 2011. At her retirement from Merck in 2013 Thornberry held the position of Senior Vice President and Franchise Head, Diabetes and Endocrinology. While an independent consultant to the biotechnology and pharmaceutical industries, Thornberry joined the boards of directors of

Intarcia Therapeutics Intarcia Therapeutics is an American biopharmaceutical company based in Boston, MA and incorporated under the laws of Delaware. It was founded in 1995 under the name "BioMedicines" and changed to its present name in 2004. In 2013, Intarcia relocat ...

and Abide Therapeutics Both companies are involved in drug discovery targeting diabetes. As of November 1, 2015, Thornberry became CEO of Kallyope Inc. in New York City.

Research

Thornberry's research areas include

obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...

fertility Fertility is the capability to produce offspring through reproduction following the onset of sexual maturity. The fertility rate is the average number of children born by a female during her lifetime and is quantified demographically. Fertili ...

and

contraception Birth control, also known as contraception, anticonception, and fertility control, is the use of methods or devices to prevent unwanted pregnancy. Birth control has been used since ancient times, but effective and safe methods of birth contr ...

. Her work has led to the development of drug candidates including FDA-approved treatments for

. Thornberry was involved in early

enzymology Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

research on

Lisinopril Lisinopril is a medication of the angiotensin-converting enzyme (ACE) inhibitor and is used to treat high blood pressure, heart failure, and after heart attacks. For high blood pressure it is usually a first-line treatment. It is also used to ...

, an angiotensin converting enzyme (ACE) inhibitor used for the treatment of

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

. Thornberry also helped to identify Niemann-Pick C1-Like 1 (

NPC1L1 Niemann-Pick C1-Like 1 (NPC1L1) is a protein found on the gastrointestinal tract epithelial cells as well as in hepatocytes. Specifically, it appears to bind to a critical mediator of cholesterol absorption. The drug ezetimibe inhibits NPC1L1 ca ...

) as the target of

ezetimibe Ezetimibe is a medication used to treat high blood cholesterol and certain other lipid abnormalities. Generally it is used together with dietary changes and a statin. Alone, it is less preferred than a statin. It is taken by mouth. It is also ...

, an inhibitor of cholesterol absorption. In 1992, her work on proteases led to the identification of the first

, caspase-1/Interleukin-1 converting enzyme (ICE). She determined that ICE was the

cysteine protease Cysteine proteases, also known as thiol proteases, are hydrolase enzymes that degrade proteins. These proteases share a common catalytic mechanism that involves a nucleophilic cysteine thiol in a catalytic triad or dyad. Discovered by Gopal Chund ...

responsible for IL-1β processing in

monocytes Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also infl ...

. Thornberry also developed a novel method for analyzing protease specificities in combinatorial libraries of positional scanning substrates. Her work has led to the broader study of proteases in

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

. Beginning in 1999, Thornberry led the biological team for the development of Januvia™ (generic:

sitagliptin Sitagliptin, sold under the brand name Januvia among others, is an anti-diabetic medication used to treat type 2 diabetes. In the United Kingdom it is listed as less preferred than metformin or a sulfonylurea. It is taken by mouth. It is also a ...

), a once-a-day oral medication that inhibits the

(DPP-4) enzyme and improves glucose tolerance to treat

. Ann E. Weber led the corresponding chemistry team for the project. The drug was approved by the

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...

in October 2006. Janumet™, a drug combining sitagliptin and

metformin Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. ...

was also approved, in April 2007. In 2007, the research team at Merck received the Prix Galien USA award for their work on Januvia™. The Januvia™ project was the first project at Merck to be co-led solely by women and the first project co-led solely by women to win the Discoverers Award. At Kallyope Inc., drug discovery focuses on the study of the brain and the gut, examining connections between neuroscience and neural circuits and the gut and internal organs, to better understand and improve health and nutrition. Thornberry also serves on the Boards of Directors of

, which is developing diabetes medicine, and of Abide Therapeutics, which is exploring the

serine hydrolase Serine hydrolases are one of the largest known enzyme classes comprising approximately ~200 enzymes or 1% of the genes in the human proteome. A defining characteristic of these enzymes is the presence of a particular serine at the active site, which ...

family (including DPP-4) as drug targets.

Awards

* 2013, Women in STEM honoree, Liberty Science Center (LSC) * 2011, Discoverer’s Award, Pharmaceutical Research and Manufacturers of America (PhRMA), with Ann E. Weber, for work which "has been of special benefit to humankind". * 2011, Thomas Alva Edison Patent Award, Research and Development Council of New Jersey * 2010, Heroes of Chemistry Award (ACS) with Ann E. Weber and Joseph Armstrong * 2008, Alumni Lifetime Achievement Award, Muhlenberg College * 2007, Prix Galien USA award to the Merck research team for Januvia™ * 2007, Merck Directors Award for work on Januvia™ * Merck Presidential Fellowship

References

{{DEFAULTSORT:Thornberry, Nancy A. Living people Muhlenberg College alumni 21st-century American chemists American women chemists American women chief executives Year of birth missing (living people) 21st-century American women scientists