Lie Gao
Curriculum Vitae

Assistant Professor
M.D. 1984, West China University of Medical Sciences
Ph.D. 2001, Peking Union Medical College & Chinese Academy of Medical Sciences
Specialty: Neural control of circulation and autonomic function
Major Interest: (1) Regulation of Angiotensin II in the brain and spinal cord on cardiovascular activity and autonomic function in normal and disease states; (2) Regulation of Angiotensin receptors (AT1R and AT2R) expression during development and disease states.

The primary objective of this laboratory is to explore, in vivo and in vitro, molecular and cellular mechanisms underlying the regulation of Angiotensin II in the rostral ventrolateral medullar (RVLM) of brainstem and the intermediolateral column (IML) of spinal cord on cardiovascular activity and sympathetic outflow in normal and chronic heart failure (CHF) states. It is believed that the presympathetic neurons (PSNs) in the RVLM directly involve, and therefore play a crucial role, in the regulation of sympathetic outflow via a monosynaptic projection to the sympathetic preganglionic neurons (SPNs) in the IML of spinal cord. These neurons in both RVLM and IML, on the other hand, also are important in the integration and regulation of cardiovascular function and sympathetic activity by receiving input from the neurons in other brain areas or from the interneurons locally in the RVLM and IML. Various neurotransmitters and neuromodulator also play a critical role in these operations, of which Angiotensin II is our focus. The sympatho-excitation in the CHF state is closely related to disorders of the above neuronal processes in the RVLM and the IML. To clarify these mechanisms we are employing real-time RT-PCR and Western blot analysis to determine gene and protein expression of AT1R, AT2R, NOS, and NAD(P)H oxidase in RVLM and IML; gene transfer of AT2R virus and plasmid vehicles into RVLM an IML to study this receptor function and its crosstalk with AT1R; whole cell patch clamp to measure potassium channels of neuronal cells under different interventions; extracellular single unit recording of RVLM and IML to observe the neuronal activity in a rat model; and measurement of arterial blood pressure, heart rate, and renal sympathetic nerve activity to monitor cardiovascular function and sympathetic outflow. These studies are providing novel insights regarding mechanisms of sympatho-excitation in the CHF state from the molecular and genetic level, cellular electrical activity, up to whole animal physiology and pathophysiology.  The second focus of our laboratory is the significance of AT2R in pancreatic endocrine regulation.  We recently found that, in the rat, the pancreas uniquely expressed the highest AT2R protein as compared with all other tissues, with equal distribution in both islet and acinar components.  We postulate that the AT2R might represent a novel signaling pathway within β- cells to regulate insulin production and secretion. We believe that an identification of novel pathway like this will provide an insight into the islet biology as well as a new therapeutic option to diabetes.  By using the Compound 21, a new created AT2R agonist, we are determining the therapeutic benefit of AT2R activation on type 1 diabetic rats (STZ-induced diabetes), type 2 diabetic rats (Zucker Diabetic Fatty rat), and type 2 diabetic mouse (db/db mouse).

Proposed mechianisms of Sympatho-excitation in Chronic Heart Failure

Recent Publications:

1. Haack KK, Gao L, Schiller AM, Curry PL, Pellegrino PR, Zucker IH. Central Rho Kinase Inhibition Restores Baroreflex Sensitivity and Angiotensin II Type 1 Receptor Protein Imbalance in Conscious Rabbits With Chronic Heart Failure. Hypertension. 2013 Jan 2. [Epub ahead of print]. PMID: 23283363.

2. Yu L, Shao C, Gao L. Developmental expression patterns for angiotensin receptors in mouse skin and brain. J Renin Angiotensin Aldosterone Syst. 2012 Nov 30. [Epub ahead of print]. PMID: 23204186.

3. Gao J, Chao J, Parbhu KJ, Yu L, Xiao L, Gao F, Gao L. Ontogeny of angiotensin type 2 and type 1 receptor expression in mice. J Renin Angiotensin Aldosterone Syst. 2012 Sep;13(3):341-52. PMID: 22526820.

4. Fahim M, Gao L, Mousa TM, Liu D, Cornish KG, Zucker IH. Abnormal baroreflex function is dissociated from central angiotensin II receptor expression in chronic heart failure. Shock. 2012 Mar;37(3):319-24. PMID: 22258229.

5. Gao J, Zhang H, Le KD, Chao J, Gao L. Activation of central angiotensin type 2 receptors suppresses norepinephrine excretion and blood pressure in conscious rats. Am J Hypertens. 2011 Jun;24(6):724-30. PMID: 21394088.