Polina Lishko

Research Expertise and Interest

Reproductive and Developmental Biology, ion channels, Physiology of Fertilization and Early Embryo Development

Research Description

Research in Lishko Lab is focused on the cell biology of mammalian fertilization. They study the molecular mechanisms that regulate egg fertility, sperm motility and the acrosome reaction. A better understanding of these processes will lead to the development of novel approaches to control and preserve human fertility, improve the human reproductive health worldwide and advance family planning.

Current Projects

Ion channels of the flagellum. Sperm motility and their ability to find and fertilize an egg are dependent on several factors, including ion homeostasis, which is controlled by ion channels and transporters. Ion channels are specialized integral membrane proteins that form ion-conducting pores in normally non-conducting membranes. Ion channels of the sperm cell open in response to environmental cues of the female reproductive tract, thus changing conductance of the sperm plasma membrane and sperm behavior. The physiological importance of sperm ion channels has inspired numerous attempts to identify and characterize them. However, for about 20 years, these attempts had been frustrated by the inability to apply methods of contemporary biology to the sperm cells due to their small size, specific morphology and vigorous motility. The sperm patch clamp technique has, in just a few years, produced a gigantic leap in our understanding of the function of these ion channels and their role in flagellar motility. We use this method to study flagellar ion channels and to shed light on the molecular mechanisms underpinning sperm-egg interaction and the environment of the female reproductive tract during the process of fertilization. This will help us to understand more about the early beginning of life, open new avenues in the treatment of human infertility, and create a new generation of nonhormonal contraceptives.

Non-genomic steroid signaling in reproductive biology. Steroid hormones are known to exert their powerful and rapid influence via an unconventional non-genomic mechanism by interacting with their membrane receptors and altering the function of ion channels or G-protein coupling receptors. Some examples include: 1) the bronchodilatory effect of the stress hormone cortisol and other glucocorticoids; 2) activation of the TRPM3 channel in insulin-producing cells in response to pregnenolone sulfate (PS); 3) activation of translationally silent spermatozoa by progesterone; 4) onset of anesthesia in rodents in response to progesterone injection; and 5) rapid enhancement of muscle performance in athletes in response to androgens. Despite these well-documented effects, the identity of the steroid targets and the downstream pathways remain obscure. Recently, by using transcriptionally silent spermatozoa as a model, we identified the novel membrane progesterone receptor and elucidated the signaling pathway that is initiated by association of progesterone with its target. The identification of this long-sought membrane progesterone receptor of human sperm cells—the α/β hydrolase domain–containing protein 2 (ABHD2)—opened a new chapter in understanding the molecular basis of the steroid action. Monoacylglycerol lipase ABHD2 is the first evolutionarily conserved steroid-activating enzyme that hydrolyzes endocannabinoid 2- arachidonoylglycerol . Interestingly, the steroid specificity profile of ABHD2 indicates that it is activated by progesterone and PS, while testosterone and cortisol act as competitive antagonists. We found that ABHD2 is highly expressed in reproductive tissues. We combine mouse genetics, electrophysiology, biochemistry, and genome editing to elucidate the molecular basis of unconventional steroid signaling in the reproductive tissues. The precise understanding of the mechanisms by which steroid hormones govern important physiological functions is vital to developing successful treatments for many endocrine disorders. 

In the News

Beyond Hormonal Birth Control

Nearly 40 percent of women worldwide stop using birth control pills within a year – mainly due to side effects such as depression, weight gain, bleeding between periods and blood clots. Research by Polina Lishko on a non-hormonal contraceptive is showing promise as a new birth control alternative.

Five innovators join the ranks of the Bakar Fellows

Five UC Berkeley faculty innovators have been selected for the Bakar Fellows Program, which supports faculty working to apply scientific discoveries to real-world issues in the fields of engineering, computer science, chemistry and biological and physical sciences.

Featured in the Media

Please note: The views and opinions expressed in these articles are those of the authors and do not necessarily reflect the official policy or positions of UC Berkeley.
December 4, 2020
Laura Santhanam
Tens of millions of women use some form of birth control in the United States. In 2019, the number of unintended pregnancies hit an all-time low, yet still accounted for 45% of all pregnancies, according to the Brookings Institution. UC Berkeley associate professor of cell and developmental biology Polina Lishko has studied how electricity propels sperm cells toward the ovum, and wondered if the electrical currents that sperm need to tap into storehouses of mitochondria could be turned off. Could compounds and chemicals, converted into a medication, flip the switch and stop sperm from swimming?
October 6, 2020
Associated Press
Among the 21 newly minted MacArthur "genius grant" fellows is UC Berkeley cellular and developmental biologist Polina V. Lishko. The John D. and Catherine T. MacArthur Foundation will give each winner $625,000 over five years to use as they please. The Chicago-based foundation has awarded the "genius grants" every year since 1981 to help further the pursuits of people with outstanding talent. For more on this, see our press release at Berkeley News. Stories on this topic have also appeared in several sources, including Fast Company, The New York Times, and The Chicago Sun Times.
April 8, 2019
Erin Brodwin, Business Insider
YourChoice Therapeutics, a new startup "stacked with researchers from UC Berkeley," is working toward bringing to market the first hormone-free male and female birth control drug. The startup -- co-founded by associate molecular and cell biology professor Polina Lishko, assistant project scientist Nadja Mannowetz, of the Lishko lab, and Akash Bakshi, a former assistant director of Technology analysis and marketing at Berkeley -- made its debut at Silicon Valley's Y Combinator demo day last month. When Professor Lishko and Mannowetz first set out to create a new kind of birth control, they hadn't meant to develop something for men, but in the course of their research they discovered that the drug they were making could be taken by both sexes. It works by disabling sperm tails, effectively robbing the sperm of their energy, while also disabling their ability to drill into an egg to fertilize it. "The contraceptive burden has been on women for forever," Mannowetz says. "We're still using the same products our grandmothers used." Another story on this topic appeared in TechCrunch.
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