Biased Drugs: The many ways to turn “on” a receptor
Presentation Type
Oral Presentation
Abstract/Artist Statement
Type II Diabetes, formerly known as, “adult onset,” diabetes, is a disease that affects almost 10% of Americans and is expected that 40% of Americans will develop Type II Diabetes in their lifetime. Type II differs from Type I diabetes in that it is developed later in life, and though it is heavily dependent on diet and exercise, it also has a large genetic dependence as well. Patients with Type II often produce insulin, but their bodies have become resistant to it, preventing its normal function as a signal to take up glucose from the bloodstream. This ultimately leads to cells becoming starved, and if not treated, can dramatically increase the chances of patients developing heart disease and nerve damage.
A target of many Type II Diabetes drugs currently prescribed in the US is a receptor called PPARγ. These drugs desensitize the body to insulin, allowing it to be recognized as a signal for glucose uptake. Citing side effects like organ failure and weakened bones, other countries have chosen to take these prescription drugs off of the market. In the US, some drugs that target PPARγ have been taken off the market completely, and others have previously had a “black box” warning of potential side effects. Though some of these drugs are currently prescribed, there is still much room for improvement.
Here, we demonstrate that this receptor could be precisely controlled to turn, “on,” some genes but not others when the receptor is bound to certain drugs. Some drugs control genes by making the receptor interact with the cell’s transcriptional machinery; Other drugs encourage interaction of this receptor with a partner receptor; Still, others may affect the DNA sequences that the receptor recognizes. To establish these drug effects, in vitro protein interaction experiments using fluorescent probes are used to measure interactions between the receptor, transcriptional machinery partners, and DNA. All in all, we see that the binding of certain drugs encourages different interactions between the receptor and these partners. These, “biased,” drugs have the potential to turn on the genes that lead to antidiabetic effects while avoiding the activation of genes that lead to undesirable side effects.
Mentor Name
Travis Hughes
Biased Drugs: The many ways to turn “on” a receptor
UC 333
Type II Diabetes, formerly known as, “adult onset,” diabetes, is a disease that affects almost 10% of Americans and is expected that 40% of Americans will develop Type II Diabetes in their lifetime. Type II differs from Type I diabetes in that it is developed later in life, and though it is heavily dependent on diet and exercise, it also has a large genetic dependence as well. Patients with Type II often produce insulin, but their bodies have become resistant to it, preventing its normal function as a signal to take up glucose from the bloodstream. This ultimately leads to cells becoming starved, and if not treated, can dramatically increase the chances of patients developing heart disease and nerve damage.
A target of many Type II Diabetes drugs currently prescribed in the US is a receptor called PPARγ. These drugs desensitize the body to insulin, allowing it to be recognized as a signal for glucose uptake. Citing side effects like organ failure and weakened bones, other countries have chosen to take these prescription drugs off of the market. In the US, some drugs that target PPARγ have been taken off the market completely, and others have previously had a “black box” warning of potential side effects. Though some of these drugs are currently prescribed, there is still much room for improvement.
Here, we demonstrate that this receptor could be precisely controlled to turn, “on,” some genes but not others when the receptor is bound to certain drugs. Some drugs control genes by making the receptor interact with the cell’s transcriptional machinery; Other drugs encourage interaction of this receptor with a partner receptor; Still, others may affect the DNA sequences that the receptor recognizes. To establish these drug effects, in vitro protein interaction experiments using fluorescent probes are used to measure interactions between the receptor, transcriptional machinery partners, and DNA. All in all, we see that the binding of certain drugs encourages different interactions between the receptor and these partners. These, “biased,” drugs have the potential to turn on the genes that lead to antidiabetic effects while avoiding the activation of genes that lead to undesirable side effects.