Ursula H. Winzer-Serhan, PhD

Education and Training

• University of Bremen, Germany, PhD, Cell Biology, 1989
• U.C.-Irvine, Research Associate, Dept. of Pharmacology

Research Interests

• The Serhan Lab is interested in the expression, physiology, function and pharmacology of nicotinic acetylcholine receptors (nAChRs) and their roles throughout life, spanning from prenatal development to old age. Nicotinic receptors are widely expressed in the peripheral and central nervous systems, in muscle fibers and immune cells. Consequently, drugs targeting nAChRs, such as the mild stimulant nicotine, the paralyzing snake toxin cobratoxin, or positive allosteric modulators designed for neurological disease treatment, can exert profound influences on brain, muscle, and immune functions. In the right context, nicotinic drugs hold great medicinal potential in mitigating age-related neurodegeneration, addressing cognitive decline, or managing symptoms associated with neurological conditions like schizophrenia. However, nicotinic drugs can have detrimental effects on autonomic functions, and particularly during critical developmental periods when essential neurodevelopmental processes take place.
• In my lab we are currently working on two different, but related projects centered around nAChRs: A) Consequences of developmental exposure to nicotine. Understanding the complex mechanisms underlying the enduring effects of prenatal nicotine exposure on behavior, notably the increase in anxiety-like behavior, and on neurophysiological changes including heightened excitatory neurotransmission and loss of nicotinic control over inhibitory GABA transmission, is a high priority in the lab. This is particularly important with regards to potentially increased vulnerability to anxiety, depression and addiction disorders.
• We use different approaches to entangle potential mechanisms. 1) traditional electrophysiological recording methods to assess neuronal activity in brain slices. 2) Cutting edge imaging approaches with genetically encoded fluorescent sensors for calcium and dopamine to determine neuronal and astrocytic activities (GCaMP6) and transmitter release (GRABDA for dopamine) in behaving animals with concurrent IV drug self-administration using a new wireless fiber-photometry set up. In addition, imaging in acute brain slices is used. B) Characterization of the Df[h15q13]/+ mouse model of the human 15q13.3 microdeletion syndrome. This microdeletion is characterized by heterozygous loss of 6 protein coding genes one of them is the CHRNA7 coding for the alpha7 nAChRs. This hemizygous microdeletion is the highest known genetic risk factor of idiopathic generalized epilepsy. The Df[h15q13]/+ mouse model replicates the behavioral phenotypes and also exhibits the characteristic hyper-excitability and is a clinically highly relevant model. The characterization of the mouse model is very critical to better understand environmental factors that determine the highly variable 15q13.3 microdeletion associated phenotype, which we are currently addressing.
• Alpha7 nAChRs are known regulators of neurotransmission and the anti-inflammatory cholinergic pathway. We use a variety of different approaches to characterize the Df[h15q13]/+ mouse model including anatomical, behavioral and electrophysiological methods. We verified increased brain hyperexcitability and susceptibility to epileptic seizures. In addition, we characterize altered neuro-immune responses to peripheral immune challenges in Df[h15q13]/+ compared to wildtype. Increased release of brain immune mediators may affect neuronal excitability and significantly contribute to seizures and epilepsy, which we addressed in collaboration with Dr Samba Reddy and his lab.