PI Information

Address

Departments of Biology & Chemistry
Julio García Díaz 111, 114, 115
University of Puerto Rico
PO Box 23360
San Juan, Puerto Rico 00931-3360
JGD Laboratory: 787-764-0000 ext 88125, 88126, 88127, 88128
Molecular Science Research Center
Lab: 223-224
Phone: 787-523-5325

https://www.upr.edu/CiCiM
e-mail: jlasalde@gmail.com / jose.lasalde@upr.edu
https://www.nachrs.org/
https://www.cifupr.org/

Education

Post-Doctoral Training

Other Training

Academic Appointments

Other Professional Appointments & Major Visiting Appointments

Awards & Honors

Major Committee Assignments

Major Research Interest (see https://nachrs.org/projects.html):

Acetylcholine receptor structure and function, lipid-protein interactions in biological membranes, neuronal acetylcholine receptor and nicotine addiction, electrophysiological analysis of slow-channel congenital myasthenic syndromes (SCCMS) associated with point mutations in the genes encoding acetylcholine receptor subunits. Molecular basis for neuronal nicotinic receptor upregulation: potential implications in HIV associated dementia.

Research Funding Information

Past

1988-1991: National Institute of Health MARC Postdoctoral fellowship, “Membrane cholesterol affects acetylcholine receptor-channel function. ($90,000)

1992-1996: National Institute of Health NIGMS Postdoctoral fellowship, “Mutagenesis of nicotinic acetylcholine receptor-channel function. ($200,000).

7/97-7/99 National Science Foundation-EPSCOR- 7/97 to 7/99, P.I., “Molecular basis of Neuronal Acetylcholine receptor desensitization” ($146,000) (Principal Investigator).

1/99-12/2001, National Institute of Health ²Postdoctoral Research Supplement” 5/1/997- 4/30/2002 ($223,000) (Principal Investigator José A. Lasalde Dominicci, Co-PI Mark McNamee UC Davis).

6/2000-8/2004,“General anesthetic interaction with lipid-exposed domains of the acetylcholine receptor”. period: 6/2000-8/2004 National Institute of Health-NIGMS-SCORE. Principal Investigator: José A. Lasalde Dominicci, Type: Institutional Minority Training Grant SCORE program NIGMS NIH MBRS S06 GM08102, cost $595,482. The goal of this project is to define the allosteric sites of the M4 trasmembrane segment of the Torpedo AChR. This project focus on the interaction of general anesthetics with lipid exposed mutations on the M4 domain an also the analysis of 3 lipid exposed allosteric positions.  Principal Investigator: José A. Lasalde Dominicci, Ph.D. Type: Institutional Minority Training Grant SCORE program NIGMS (NIH MBRS S06 GM08102) .

01/01/1999-7/31/2004, “Acetylcholine receptor genes in slow-channel syndrome” ($1,400,000) Consortium Agreement Period: January 1, 1999 to July 31, 2004, Type: National Institute of Health-(2RO1-N33202) C0-P.I (Principal Investigator- Christopher Gómez, J.A. Lasalde-Dominicci Co-Principal Investigator). The goal of this project is to understand the pathophysiology and molecular mechanisms involved in the impairment of neuromuscular transmission in the slow channel congenital myasthenic syndrome (SCCMS).   Consortium agreement with University of Minnesota.

6/2000-7/2002. “Development of pathogenic Neuronal Nicotinic Acetylcholine receptor models” Postdoctoral Research training Supplement NIH, American Psychiatry Association ($80,000) (Principal Investigator Maria Reyes, M.D., Co-Investigator: José A. Lasalde Dominicci.  The long-term goal of this project is to develop transgenic mice models for pathogenic cholinergic pathways in the CNS. The proposed research will focus on the construction and electrophysiological characterization of two pathogenic mutations recently found in the muscle type AChR (b1V229F and a1V249F) at homologous positions in the α4 neuronal subunit. These two mutations have been found in two myasthenic patients with the slow-channel (SCCMS).

7/2000-8/2003, “Molecular Basis of neuronal nicotinic receptor up-regulation and nicotine addiction” ($30,000). The goal of this research proposal is to combine electrophysiological, biochemical, molecular biological techniques and confocal imaging in order to define the structural and functional basis for the relationship between up-regulation and desensitization of the α4β2 nAChR induced by nicotine.  The mechanism by which the a4b2 nAChR number is increased in the cell surface following nicotine exposure is thought to involve reduced turnover of receptors, it has been suggested that a conformational change of the receptor prevent it from being removed from the cell surface.  The long-range goal of the proposed experiments is to gain insight into a mechanism of upregulation of the a4b2 nAChR up-regulation that has been associated to nicotine tolerance and dependence. Principal Investigator: José A. Lasalde Dominicci, Ph.D. Type: Institutional Funds (FIPI) (Years 2000-2003) Period: July 1, 2000 to December 31, 2003.

10/1998-12/2000, “Instrumentation for Confocal microscope” Principal Investigator: José A. Lasalde Dominicci, Ph.D. Type: Competitive Instrumentation NIH-NCRR (1S10RR 13705-01). This project provided Confocal Laser Scanning microscope. This system includes Krypton/Argon mixed gas laser with lines 488, 568 and 647nm; scanning imaging head; fiberoptics laser delivery; three detector channels; multichannel data acquisition; Pentium based scan control and image acquisition system. Funds awarded $236, 433.

10/1999-8/2000, “Confocal Imaging Facility Upgrade” Principal Investigator: José A. Lasalde Dominicci, Ph.D. Type: Instrumentation, National Science Foundation EPSCoR. This proposal up-grades the confocal imaging facility with an additional inverted microscope (coupled to the Zeiss 510 NLO confocal microscope) and computers programs and printers to support image analysis. Funds awarded $226,000.

10/1998-10/1999, “Automated DNA sequencing instrumentation Facility” NSF-EPSCoR Shared Instrumentation grant, Awarded (3/15/1999)  Principal Investigator: Owen McMillan, Ph.D. Co- Investigator: José A. Lasalde Dominicci, Ph.D. Funds awarded $165,000.

5/1999-8/2000, “A twophoton laser application for confocal imaging” NSF EPSCoR co-funding Principal Investigator: Fernando Santana, Ph.D., Co-Principal Investigator: José A. Lasalde Dominicci, Ph.D. Funds awarded $232,000

09/1997-04/31/2009 Type: 2R01GM56371-12, Funds awarded $2,497,000.  “Cholesterol and lipid protein interactions affect acetylcholine channel function” (Investigates the effects of cholesterol and lipid exposed mutation on the Torpedo and muscle-type AChR channel function). Principal Investigator: José A. Lasalde Dominicci, Agency National Institute of General Medical Sciences (NIGMS). The conformational transitions of the Nicotinic Acetylcholine receptor (AChR). We decoded a network of hydrophobic allosteric sites located at lipid exposed of the M3 transmembrane segment. The main hypothesis is that an exclusive group of lipid-exposed positions might play a critical role in the channel function through physical interactions with membrane lipids that remain to be defined. This research explore specific, novel aspects of the interaction of these allosteric sites with the membrane bilayer using two approaches: lipid replacements in the intact oocyte, site specific mutagenesis of the M3 transmembrane domain of the Torpedo and muscle-type AChR and the use of nonsense suppressor methods to deliver unnatural amino acids to novel allosteric positions in transmembrane segments.

6/2004-8/2008, “Mutagenesis of nicotinic acetylcholine receptors”. period: 6/2004-8/2008 ($740,000) National Institute of Health-NIGMS-SCORE. Principal Investigator: José A. Lasalde Dominicci, Type: Institutional Minority Training Grant SCORE program NIGMS NIH MBRS S06 GM08102, cost $595,482. The goal of this project is to define the allosteric sites of the M4 trasmembrane segment of the Torpedo AChR. This project focus on the interaction of general anesthetics with lipid exposed mutations on the M4 domain an also the analysis of 3 lipid exposed allosteric positions.  Principal Investigator: José A. Lasalde Dominicci, Ph.D. Type: Institutional Minority Training Grant SCORE program NIGMS (NIH MBRS S06 GM08102).

9/2009-11/2012 Principal Investigator: José A. Lasalde Dominicci, Ph.D.  (NSF), Type: MRI Instrumentation Grant, “Emission-Fingerprinting upgrade-Confocal and Two photon Facility–Multi Campus Initiative-UPR” Submitted January 28, 2009.  The main goal of this proposal is to upgrade the applications of an existing Confocal and Two-Photon Microscopy Facility of the University of Puerto Rico (UPR), Río Piedras Campus (www.cifupr.org), to perform fluorescence emission fingerprinting – Budget allocation: $322,000.

1/2010-7/2015 Type 2RO1-N33202 “Acetylcholine receptor genes in slow-channel syndrome” ($1,400,000.013) Consortium Agreement: National Institute of Health (Principal Investigator- Christopher Gómez, J.A. Lasalde-Dominicci Co-Principal Investigator). The goal of this project is to understand the pathophysiology and molecular mechanisms involved in the impairment of neuromuscular transmission in the slow channel congenital myasthenic syndrome (SCCMS). Consortium agreement with University of Chicago.

10/2006-8/31/2013 – No Cost Extension – SNRP: “Specialized Neurosciences Research Program in NeuroAIDS”, ($1,500,000 per year) Principal Investigator: Edmundo Kraiselburd, Scientific Director, José A. Lasalde Dominicci (time effort 25%, Scientific Director). National Institute of Neurological Disorder and Stroke (U54NS0430311), National Institutes of Health. The present NeuroAIDS Program of the UPR-MSC SNRP funded by NINDS provides the ideal instrument to upgrade the level of research in HIV and neuroscience’s building on these existing clinical and basic research infrastructures and the collaboration with NIH funded scientists with skills and expertise otherwise not available in Puerto Rico. (for further information see http://snrp.rcm.upr.edu/investig.html.

10/2006-8/31/2013- No Cost Extension, – SNRP, NIH- U54NS0430311-NCE; Title: “Molecular basis for neuronal nicotinic receptor upregulation: potential implications in HAD” NCE P.I. José A. Lasalde-Dominicci, Direct Cost $350,000 per year (5 years) 11/2006-10/2013.  In the project, we will use voltage-clamp whole-cell current electrophysiological recording to assess nAChR function, radioligand binding assays to ascertain numbers of a4b2-nAChR in total cell membranes and on the cell surface, site-directed mutagenesis approaches, and confocal microscopy to study the upregulation of the a4b2 and a7 nAChRs.  The aims are to: (1) define the structural and functional basis for the up-regulation of the a4b2 nAChR induced by chronic nicotine exposure, (2) develop methods to incorporate fluorescent amino acids into the nAChR subunits using nonsense suppressor techniques that will allow the study nAChRs trafficking in vivo, (3) gain insight into the molecular basis for the upregulation of the a7 nAChR induce by a combined treatment with HIV-1 gp120, nicotine and galantamine in vitro, (4) examine the functional state of the a7 nAChR after chronic exposure to gp120 in macrophages from HIV infected patients and (5) express and purify the a7 nAChR extracellular domain for crystallization trials.

Grant Number P20 RR-016470 from the National Center for Research Resources (NCRR), Period: 05/01-2009-04/31-2014. P.I. Vibha Bansal, Ph.D “Screening of different sources of plasminogen activators, their inhibitors and development of new techniques for isolation of plasminogen activators”, José A. Lasalde Dominicci, Ph.D. (in kind as Collaborator/Mentor).

Grant Number P20 RR-016470 from the National Center for Research Resources (NCRR), Period: 05/01-2009-04/31-2014. Margarita Ortiz, Ph.D., PI Project, José A. Lasalde Dominicci, Ph.D. (in kind Collaborator/Mentor) – “Novel synthesis of nicotinic agonists for Alzheimer’s therapy”\

NIH Clinical Grant Award $50K, PI Dr. Carlos Báez. Mentor, Dr. José Lasalde Dominicci “Bupropion as adjunctive therapy to improve immune profile in HIV seropositive smokers”, Awarded 02/11/2011 (in kind Mentor)

Clinical Bioreagent Center in PR.  HIV Vaccine pilot project CRD OISE-14-60-828-01, 06/15/2015-01/15/2016 (José A. Lasalde Dominicci, Ph.D. PI 5% in kind)

Present Funding

P30GM149367 NIH/NIGMS (Dr. Lasalde-Dominicci, PI/PD), Title: “UPR COBRE Center for Neuroplasticity” (UPR-CCfN) The specific aims of this COBRE are to: 1) Foster development of junior investigators into competitive researchers working on projects with direct biomedical significance. An intensive mentoring program will be implemented with the goal of creating a “culture of research” comparable to that of major research-intensive universities. 2) Provide a Neuroimaging and Electrophysiology Facility (NIEF) that will offer state-of-the-art instrumentation, training, and expertise to the neuroscience community of Puerto Rico. 2) Provide a Neuroimaging and Electrophysiology Facility (NIEF) that will offer state-of-the-art instrumentation, training, and expertise to the neuroscience community of Puerto Rico. Awarded on July 15, 2023 Total Award Amount: $5,558,315 (https://newsismybusiness.com/upr-neuroplasticity-center-receives-more-than-5m/)

C06 OD035989-01 NIH/NIGMS (Dr. Lasalde-Dominicci, PI/PD), “UPR Center for Incubator and Technology Transfer (UPRCITT)” The goal is to create the UPR Center for Incubator and Technology Transfer at the University of Puerto Rico (UPRCITT) for entrepreneurial collaborative scientific research and graduate education in multiple disciplines. To achieve the UPRCITT, we will fit out one floor, 20,000 net square feet, in the eight-story UPR Molecular Sciences Research Center (MSRC, http://cicim.upr.edu/) shell constructed in San Juan, Puerto Rico. The UPRCITT floor will include GLP/cGMP research facilities as well as flexible laboratory spaces for transitioning basic research concepts into pilot commercial projects. The main goals of the UPRCITT are: (1) to enhance PR’s economic development by founding an innovation ecosystem that will stimulate the creation and incubation of start-up companies by providing cGMP state-of-the-art laboratories and CORE facilities, (2) to promote collaborations among Biotech and Pharmaceutical companies and UPR researchers, and (3) to provide workforce development by training for faculty, underrepresented undergraduate/graduate students and postdoctoral fellows to work in teams in an innovation ecosystem which will promote the culture of entrepreneurship in PR. Awarded on September 2, 2023. Total Award Amount: $7,898,000. (https://newsismybusiness.com/upr-receives-7-8m-grant-from-nih-for-molecular-sciences-and-research-center/).

U54 Supplement- P20-5U54CA096300-17- NCI/NIH(Dr. Lasalde-Dominicci, an Dr. Manuel Delgado, MPI) “The Role of Acetylcholine Receptors in Merkel Cell Polyoma Virus-induced Merkel Cell Carcinoma”, New Project in collaboration with Dr. Phyu P. Aung, MD Anderson Cancer Center. The objective of this project is to characterize the expression of neuronal nicotinic acetylcholine receptors (nAChRs) in a large cohort of patients with Merkel Cell Carcinoma tumors by confocal imaging, immunohistochemistry and RT-PCR and to correlate the expression pattern with immune infiltrate, genome methylation, and clinical and demographic characteristics. Project grant period 09/01/2022- 08/31/2024 – $ Total Award Amount: $170,000.

2P20GM103642 NIGMS/NIH (Dr. Lasalde-Dominicci, PI/PD), – Equipment Supplement- for the COBRE Center for Neuroplasticity: (1) Nikon Eclipse LV100N Polarized microscope, (2) Cytiva AKTA Purifier 100 FPLC System (3) LI-COR Odyssey Western Blot system and (4) QuantStudio 3 PRO-Real Time PRC system. Awarded on May 5, 2023. These instruments are available now at the UPR-CCfN (https://cobrepr.com/), located in floor 6 of the MSRC. $ Total Award Amount: $250,000.

COVID 19 funds ARPA initiative DDEC. (Dr. Lasalde-Dominicci, and Dr. Manuel Delgado, MPI)- “Understanding the cholinergic anti-inflammatory response in the context of SARS Cov-2: Uncovering a potential therapeutic strategy to counteract the cytokine storm in COVID-19”. This proposal aims to investigate the role of the alpha7-neuronal nicotinic receptor and the cholinergic anti-inflammatory pathway (CAR) in the regulation of inflammation in COVID-19 patients. Awarded on September 20, 2023. $ Total Award Amount: $250,000.

Collaborative Research Projects

FOUNDER – UPR Cinical Bioreagent Center (CBC)

Patents Awarded

Two new patent applications in 2023:

1. A continuation-in-part (CIP) patent application entitled “A lithographic
RMP@LMx V.2 and V3 device for membrane protein crystallization” for the
protection of a Lithographic version device filed on April 11, 2023.

2. A Provisional Patent application. Filing Receipt – Serial No. 63459620
(Guanosine Microparticles for Vaccine Optimization, Method of Synthesis and
Applications Thereof) filed on April 14 2023.

This CV is condensed. For full CV click here.