An assistant professor in the department of biochemistry discussed his work on membraneless organelles and their interactions with hormones like androgen and estrogen in the body at the Oct. 26 “Spatial Gene Regulation by Nuclear Organelles” biology department event.
Sreejith Nair presented his work as part of an ongoing seminar series by the biology department. Nair’s research works to uncover the specialized processes through which membraneless organelles form. Organelles are specialized structures within cells that perform functions related to metabolism, growth and gene expression; while some are membrane-bound and exist within the cytoplasm of the cell, Nair focuses solely on those without a membrane.
Nair said understanding the chemical signaling pathway of estrogen with respect to these membraneless organelles is the first step to finding new treatments for hormone-based cancers.
“The transcription factor that regulates estrogen is a huge driver of breast cancer,” Nair told The Hoya. “Understanding this signaling pathway and how it works in any detail will have an immediate impact in how we understand breast and ovarian cancer and how we develop treatment.”
Ronda Rolfes, the chair of the department of biology and the host of the seminar, said Nair’s research on the forming of condensates is similar to the mechanism of separating liquids in a mixture.
“One analogy is to think about how oil and water separate in a salad dressing. When you shake them, you form these small little droplets that are separated from the other environment,” Rolfes told The Hoya. “That’s the principle that’s happening within the nucleus. There are small microenvironments that differ from the aqueous environment surrounding them.”
According to Nair, current hormone-blocking treatments for cancer are being outpaced by the body’s resistance to them, and individual gene mutations inside cells can cause changes to the creation of condensates within such cells. This increases the cell’s ability to bind to estrogen and increases the proliferation of hormone-influenced cancers. Nair said understanding the changes in cell-estrogen receptors should allow for the creation of more comprehensive treatments to certain cancers.
“One of the primary therapeutic approaches to treat breast cancer is to block estrogen pathways using drugs. One drug is called tamoxifen, which is the most commonly used drug,” Nair said. “The issue is that many people develop resistance particularly against tamoxifen. We want to find out whether mutations in genes change the physical properties of condensates and whether the tamoxifen is changing their gene expression.”
Anqi Feng (CAS ’24), a student researcher in the Nair lab, said condensates play a role in changing RNA sequences and the copying of DNA information to RNA.
“Membraneless organelles are very crucial for important biological processes in the nucleus like RNA splicing, but most importantly their regulation of gene transcription,” Feng told The Hoya. “In some cancer cells, the transcription mechanisms were triggered in a specific way.”
Xinrui Wei, a research assistant at the Nair lab, said genes are the key to understanding protein formation in membraneless organelles. A gene knockout is the process of using technology to delete or deactivate a sequence of genetic information.
“We try to target the specific protein to see the function of it in the cancer cells,” Wei said. “So we basically knock out the gene to see how it affects cell function.”
Feng said the survival motor neuron (SMN) and coilin are two formative proteins for creating condensates. When transcribed, these proteins are likely implicated in estrogen pathways that contribute to cancer.
“In the lab, we focus on membraneless nuclear organelles, specifically two proteins called SMN (Survival Motor Neuron) and coilin, which are responsible for producing nuclear speckles and Cajal bodies,” Feng said. “Our aim is to study these proteins and especially their functions and hormone-induced transcription.”
Cajal bodies and nuclear speckles are membraneless organelles that play roles in RNA synthesis and manipulation. These are two examples of condensates being studied in Nair’s lab that could have an impact on hormone binding and consequently breast cancer.
Rolfes believes that more research on condensates will be formative for treating an assortment of cancers even besides breast and ovarian variants and that the Nair lab offers a new door for oncology innovations.
“Our increased understanding of the molecular world will allow us to make new interventions that might be helpful to disease or cancer,” Rolfes said. “Understanding fundamental biological and biochemical principles that underlie cancer later on can give us insights into new treatments and ways of approaching it.”