Fernando Gonzalez
University of California, San Francisco University of California, San Francisco
University of California, San Francisco
CURRICULUM VITAE
Name:
Fernando F Gonzalez, MD
Position:
Associate Professor of Clinical Pediatrics, Step 3
Pediatrics
School of Medicine
EDUCATION
1993 - 1997
Brown University, Providence, RI Sc.B.
Neuroscience
1997 - 2001
Brown University School of
Medicine
M.D.
2001 - 2002
Harbor-UCLA Medical Center,
Torrance, CA
Intern
Pediatrics
2002 - 2004
Harbor-UCLA Medical Center
Resident
Pediatrics
2004 - 2007
University of California, San
Francisco
Post-doctoral
fellow
Neonatal-Perinatal
Medicine
LICENSES, CERTIFICATION
2002
Medical licensure, California
2002
Drug Enforcement Agency Licensure
2005
Certified, American Board of Pediatrics
2008
Certified, Neonatal-Perinatal Medicine
PRINCIPAL POSITIONS HELD
2007 - 2015
University of California, San Francisco
Assistant Adjunct
Professor
Pediatrics
2015 - present University of California, San Francisco
Associate
Professor of
Clinical Pediatrics
PediatricsPrepared: May 3, 2021
2 of 27
2015 - present University of California, San Francisco
Co-Director,
Neuro-Intensive
Care Nursery
Pediatrics
2019 - present University of California, San Francisco
Director,
Molecular
Medicine
Pathway
Pediatrics
OTHER POSITIONS HELD CONCURRENTLY
1996 - 1996
Stanford University
Research
Assistant
Division of
Anesthesiology
1998 - 1998
Brown University
Research
Assistant
Division of
Surgical
Research
2002 - 2003
Harbor-UCLA
Research
Assistant
Division of
Pulmonary
Research
2019 - present National Pediatrician-Scientist
Collaborative Workgroup
Member
HONORS AND AWARDS
1998
Program in Liberal Medical Education
Research Fellowship
2004
Harbor-UCLA Pediatric Residency
Teaching Award
2005
NIH Loan Repayment Program for
Pediatric Research
KEYWORDS/AREAS OF INTEREST
Neonatal brain injury, neuroprotection, stroke, hypoxic-ischemic encephalopathy,
neurogenesis, stem cell plasticity, erythropoietin, cell fate
CLINICAL ACTIVITIES
CLINICAL ACTIVITIES SUMMARY
Clinical service: 8 weeks/year in the Intensive Care Nursery at UCSF Mission Bay; 32
overnight calls per year. Responsibilities include directing clinical care of neonates admitted to
the Neuro-Intensive Care Nursery with diagnosed or suspected brain injury, as well as
supervising housestaff in the care of premature and full-term neonates with congenital
anomalies requiring surgical intervention or ECMO.Prepared: May 3, 2021
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CLINICAL SERVICES
2007 - present Attending Physician, Intensive Care Nursery, UCSF
6-8 weeks per
year, 28-40
overnight calls
PROFESSIONAL ACTIVITIES
MEMBERSHIPS
2001 - present American Academy of Pediatrics
2001 - present California Medical Association
2009 - present Society for Neuroscience
2013 - present Western Society for Pediatric Research
2014 - present Dana Alliance for Brain Initiatives
2016 - present Society for Pediatric Research
2019 - present National Pediatrician-Scientist Collaborative Workgroup
SERVICE TO PROFESSIONAL ORGANIZATIONS
2014 - present WSPR
Abstract reviewer,
moderator
2014 - present PAS
Abstract reviewer,
moderator,
discussant
2015 - present International Neonatal Consortium: Seizure Workgroup
Co-Leader
2016 - 2016
Cerebral Palsy Alliance: Neonatal Stroke Summit
Chair
2020 - 2023
SPR Fellows Basic Research Awards Selection Committee
SERVICE TO PROFESSIONAL PUBLICATIONS
2006 - present Ad hoc reviewer for Journal of Cerebral Blood Flow and Metabolism
2007 - present Ad hoc reviewer for Archives of Disease in Childhood
2007 - present Ad hoc reviewer for Journal of Neuroscience Research
2007 - present Ad hoc reviewer for Pharmacological Research
2008 - present Ad hoc reviewer for Developmental Neuroscience
2009 - present Ad hoc reviewer for Pediatric Research
2012 - present Ad hoc reviewer for Journal of Neuroscience
2013 - present Ad hoc reviewer for Science Translational Medicine
2013 - present Ad hoc reviewer for NeurosciencePrepared: May 3, 2021
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2013 - present Ad hoc reviewer for Acta Neurobiologiae Experimentalis
2013 - present Ad hoc reviewer for Neurological Research
2013 - present Ad hoc reviewer for Glia
2013 - present Ad hoc reviewer for PLoS ONE
INVITED PRESENTATIONS - INTERNATIONAL
2010
Pediatrics Grand Rounds, Vietnam National Hospital of
Pediatrics. "Protecting the Newborn Brain." Hanoi, Vietnam
2012
Hershey Developmental Brain Injury Conference. "Is
Erythropoietin the Answer?" London, England.
2013
West China Second University Neonatology Symposium.
Chengdu, China.
2016
NNCC SIG at PAS. Neuromonitoring. Baltimore, MD, USA.
2016
Cerebral Palsy Alliance: Neonatal Stroke Summit. Santa
Monica, CA, USA
2017
NNCC SIG at PAS. "NIRS Monitoring in the NICN". San
Francisco, CA, USA.
2017
PAS. Neonatal Neurocritical Care Workshop. San Francisco,
CA, USA
2018
Hershey Developmental Brain Injury Conference.
"Angiogenesis and neurogenesis after neonatal stroke."
Asilomar, CA
2019
EpicLatino Network. Cell death mechanisms in neonatal brain
injury. Bogota, Colombia. "Neurocritical Care in the Nursery:
HIE and Stroke." AND "Cell Death Mechanisms and Repair
after Neonatal Brain Injury."
2019
Il Neonatal Neurology Symposium. Mexico City, Mexico.
"Neurocritical Care of the newborn, neuroimaging, and
determinants of long-term outcomes after hypoxic-ischemic
encephalopathy." AND "Combined treatment with
erythropoietin and hypothermia for hypoxic-ischemic
encephalopathy."
2020
Congreso Nacional de la Sociedad Mexican de Neurologia
Pediatrica. Queretaro, Mexico.
2020
Neo Garrahan, 10th edition: The Brain of the Newborn.
“Neurocritical Care in the Nursery: Neuroimaging and
outcomes after encephalopathy” AND “New treatment
strategies for HIE and stroke”Prepared: May 3, 2021
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INVITED PRESENTATIONS - NATIONAL
2011
CIRM Workshop: Newborn Neurological Disorders Leading
to Cerebral Palsy. The roles of hypothermia and
erythropoietin in neonatal brain injury and repair. San
Francisco, CA
2012
NINDS/ANA Career Development Symposium. Boston, MA.
2018
Innovations in Neonatal Care. The Benefit of a Neuro-NICU.
Houston, TX.
INVITED PRESENTATIONS - REGIONAL AND OTHER INVITED PRESENTATIONS
2004
Pediatrics Grand Rounds, Harbor-UCLA Medical Center.
Clinical Case Conference: Juvenile Dermatomyositis.
Torrance, CA
2008
Neonatal Clinical Physiology Laboratory, UCSF.
Hypoglycemia in the newborn
2008
Resident Conference, UCSF. Antibiotics in the ICN;
Pulmonary Hypertension; Neuroprotection of the Newborn;
Therapeutic Hypothermia
2012
Resident Conference, UCSF. EPO: Bench to Bedside.
2012
PICU/ICN Research Conference, UCSF. The role of
erythropoietin in neurogenesis and repair after neonatal
stroke.
2012
Fellows College, UCSF. How to develop your scholarly
research focus.
2013
Pediatrics Grand Rounds, Marin General Hospital.
Neuroprotection of the Newborn. Greenbrae, CA
2014
Pediatric Critical Care Conference, John Muir Hospital.
Approach to the Brain Injured Infant. Walnut Creek, CA
2015
Neonatology Research Conference, University of Washington
and Seattle Children's Hospitals. Neurogenesis After
Neonatal Stroke - Can We Enhance Endogenous Repair
After Early Brain Injury? Seattle, WA
GOVERNMENT AND OTHER PROFESSIONAL SERVICE
2013 - present INSERM
Grant reviewer
2013 - present Cerebral Palsy Alliance
Grant reviewer
2014 - present Italian Ministry of Health
Grant reviewer
2018 - present Medical Research Council, UK
Grant reviewerPrepared: May 3, 2021
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UNIVERSITY AND PUBLIC SERVICE
SERVICE ACTIVITIES SUMMARY
My services to the University have been focused on the School of Medicine and the
Department of Pediatrics. For the School of Medicine, in addition to becoming a DEI
Champion, I have been focused on UIM medical students and working directly with them
through the UCSF UIM Mentor Match Family program. For the Department of Pediatrics, I was
chosen to lead the Molecular Medicine Pathway, focused on individualizing the education and
training for future pediatric physician-scientists at UCSF. I also play a significant role in the
Pediatrics Intern Selection Committee meetings and interview process. For the last two years, I
have also given research talks and participated in mentorship programs for premed students at
UC Berkeley.
UNIVERSITY SERVICE
UC SYSTEM AND MULTI-CAMPUS SERVICE
2019 - present Diversity, Equity and Inclusion
Champion
UCSF CAMPUSWIDE
2020 - present Limited Submission Program - Grant Review Committee
Reviewer
SCHOOL OF MEDICINE
2019 - present UCSF UIM Mentor Match Family
Group leader
DEPARTMENTAL SERVICE
2006 - 2007
FLAG - Pediatric Fellows Leadership Advocacy Group
2007 - 2008
Task force on setup room practices and neonatal
resuscitation
2007 - present Neurological Intensive Care Nursery
Director
2011 - 2017
Fellowship Selection Committee for Neonatal-Perinatal
Medicine
2014 - 2016
Clinical Competency Committee, Division of Neonatology
2014 - 2016
Neonatal-Perinatal Research Incentive Planning Committee
2015 - present Pediatrics Diversity Committee
2017 - present Pediatrics Intern Selection Committee
2018 - present Neonatal Neurology Fellowship Selection Committee
2019 - present Pediatric Molecular Medicine Pathway
Director
2020 - present Departmental K12 Program - Internal Advisory Committee
SERVICE AT OTHER UNIVERSITIES
2017 - present Premed@Berkeley, Phi Delta Epsilon, Stem Cell guest
speaker and mentorship program
UC BerkeleyPrepared: May 3, 2021
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CONTRIBUTIONS TO DIVERSITY
CONTRIBUTIONS TO DIVERSITY
DEI Champion
TEACHING AND MENTORING
TEACHING SUMMARY
One of my primary responsibilities is teaching medical students, residents, nurse practitioners
and neonatology fellows about neonatal physiology, pathophysiology, and care of newborns.
This involves teaching medical students, residents, nurse practitioners and neonatology fellows
about neonatal physiology, pathophysiology, and overall care of newborns in both formal
conference presentations and informal didactic sessions. As Co-Director of the Neuro
Intensive Care Nursery (NICN) with Dr. Hannah Glass, we have developed a formal curriculum
regarding brain-focused care in at risk neonates, which centers on hypothermia,
neuromonitoring, neuroimaging, and neurodevelopmental outcomes. We run a “boot camp” for
incoming neonatology and child neurology fellows, neonatal hospitalists and neonatal nurse
practitioners in July of each year. Now, as the Pediatric Molecular Medicine Pathway Director, I
have created and organized a curriculum of formal teaching for the Molecular Medicine
Pathway pediatrics residents for their 2-week cohorted elective to begin later in 2020. This is
focused on career development, mentoring, teaching, management of team dynamics and
leadership development.
FORMAL TEACHING
Academic Yr Course No. & Title
Teaching Contribution
School
Class
Size
2015 -
present
Intro to the Neuro
Intensive Care
Nursery
Developed a core curriculum
of neurocritical care in the
newborn, including
neuromonitoring, imaging,
neuroprotection focused on
full-term infants, premature
infants, and those born with
congenital cardiac disease.
Medicine
Incomi
ng
residen
ts and
fellows
in
Pediatr
ics and
Child
Neurol
ogyPrepared: May 3, 2021
8 of 27
Academic Yr Course No. & Title
Teaching Contribution
School
Class
Size
2020 -
present
Molecular Medicine
Curriculum
2-week cohorted elective
focused on mentorship,
career development,
leadership, and personal
development
Medicine
Include
s
current
MM
pathwa
y
Pediatr
ics
residen
ts
(curren
tly 8)
INFORMAL TEACHING
2004 - present Bedside and didactic teaching rounds, Intensive Care Nursery
MENTORING SUMMARY
My clinical expertise enables me to provide guidance and advice to trainees focused on
pursuing careers as neonatologists or neonatal neurologists, while my experience as a basic
science-translational researcher allows me to interact with mentees who desire a career in
basic science and translational research while working in a clinical environment. In addition,
my role as a PI allows me to mentor doctoral candidates, post-doctoral researchers, SRAs and
students in my lab and within the larger Neonatal Brain Disorders laboratory. I regularly speak
to the Pediatrics fellows at the formal Fellows College Program on obtaining funding and
scholarship oversight. I have been on the Scholarship Oversight Committee for multiple past
and current pediatric subspecialty fellows. Finally, I now have the opportunity to mentor
Pediatrics residents in the Molecular Medicine Pathway. This is focused not just on career and
leadership development, but also working individually with each of these highly motivated
residents to find the best clinical and research pathway, mentors, and plan to enable their
successful career transition to eventually become physician-scientists. I also mentor students
through the Brown University Physicians-in-Action program, allowing minority students to
shadow me in the clinical environment, and I participate in the UCSF Underrepresented in
Medicine mentorship program.
PREDOCTORAL STUDENTS SUPERVISED OR MENTORED
Dates
Name
Program or
School
Mentor Type
Role
Current
Position
2004 - 2008
Katherine Yap Medical
student,
UCSF
Career
Mentor,Co
Mentor/Clinical
Mentor
Pediatrician,
Kaiser
PermanentePrepared: May 3, 2021
9 of 27
Dates
Name
Program or
School
Mentor Type
Role
Current
Position
2005 - present Andra Dingman Neonatal
Brain
Disorders
Laboratory,
UCSF
Career Mentor
Child
Neurologist,
Colorado
2005 - 2006
Jaqueline
Kamrath
Pediatric
Development
al Biology
Laboratory,
UCSF
Career Mentor
Psychiatrist,
New York
Presbyterian
2007 - present Vien Nguyen
PDBL, UCSF Research/Schola
rly
Mentor,Project
Mentor
Associate
Specialist,
UCSF
2009 - 2010
Lauren Wu
Medical
student,
UCSF
Career Mentor
Pediatrician
2011 - 2012
Geri Landman Medical
student,
UCSF
Career Mentor
Pediatrician
2011 - present Amara
Larpthaveesarp
NBRI, UCSF Research/Schola
rly
Mentor,Project
Mentor,Career
Mentor
Specialist,
UCSF
2011 - 2013
Grace Or
UCSF
Career Mentor
CEO, Seven
Biosciences
2013 - 2013
Dylan Denault UC Irvine
Career Mentor
Medical
student
2013 - present Meg
Georgevits
Trinity
Project
Mentor,Career
Mentor
Researcher
2013 - present Sasha
Mikhailova
UC Davis
Career Mentor
Graduate
Student
2017 - present Sam Ostrin
UC Berkeley Project Mentor
SRA
2017 - present Sarah Blaine
UC Berkeley Project Mentor
SRA
2017 - present Crystal Tse
Brown
University
Career Mentor
Medical
StudentPrepared: May 3, 2021
10 of 27
POSTDOCTORAL FELLOWS AND RESIDENTS MENTORED
Dates
Name
Fellow
Mentor Role
Faculty Role
Current
Position
2006 - 2008
Henry Cheng Pediatrics
resident,
UCSF
Assistant
Professor,
Boston
Children's
2007 - 2008
Jennifer Davis Pediatrics
resident,
UCSF
Associate
Professor,
UCSF
2007 - present Ruggero
Spadafora
Post-doctoral
researcher,
UCSF
Career Mentor
Pediatrics
Resident,
UCSF
2010 - present Sumudu
Ranansinghe
Post-doctoral
researcher,
UCSF
Research
fellow,
University of
Auckland
2009 - present Cindy Tran
Pediatrics
resident,
UCSF
Neonatologist
, ZSFGH
2012 - present Annie Fang
Neonatology
Fellow, UCSF
Research/Schola
rly
Mentor,Career
Mentor
Neonatologist
, Kaiser
Permanente
2012 - present Mark Peterson Neonatology
fellow, UCSF
Assistant
Professor,
UCSF
2012 - 2014
Eileen Foy
Infectious
Disease
fellow, UCSF
SOC member
Medical
Director, Vir
Biotechnolog
y
2012 - present Travis Vesel
Pediatric
Critical Care
fellow, UCSF
SOC member
Assistant
Professor,
Duke
2014 - present Rachael
Beckert
Pediatrics
resident,
UCSF
Neonatologist
, Kaiser
2015 - present Haiyan Sun
Post-doctoral
researcher,
UCSF
Project Mentor
ResearcherPrepared: May 3, 2021
11 of 27
Dates
Name
Fellow
Mentor Role
Faculty Role
Current
Position
2016 - present Katsuoki
Kojima
Neonatology
fellow, UCSF
Research/Schola
rly
Mentor,Career
Mentor
SOC member
Assistant
Professor,
Cincinnati
Children's
2016 - present Betsy Crouch Neonatology
fellow, UCSF
Career Mentor
Assistant
Professor,
UCSF
2017 - present Natalie Chan
Neonatal
Neurology
fellow, UCSF
Career
Mentor,Co
Mentor/Clinical
Mentor
Neonatologist
, UBC
2017 - present Srinivasa
Manideep
Chevali
post-doc,
UCSF
Research/Schola
rly Mentor
Specialist,
UCSF
2017 - present Marie-Coralie
Cornet
Neonatology
fellow, UCSF
Research/Schola
rly
Mentor,Career
Mentor
2018 - present Benjamin
Aghoghovwia
Post-doctoral
researcher,
UCSF
Research/Schola
rly
Mentor,Project
Mentor,Career
Mentor
2018 - present Jeffrey Russ
Child
Neurology
Resident,
UCSF
Research/Schola
rly
Mentor,Project
Mentor,Career
Mentor
Child
Neurology
Resident
2018 - present May Szeto
Pediatrics
Resident,
UCSF
2019 - present Matthew Kan Pediatrics
Resident,
UCSF
A/I fellow
2019 - present Melody Lun
Pediatrics
Resident,
UCSF
Neonatology
FellowPrepared: May 3, 2021
12 of 27
Dates
Name
Fellow
Mentor Role
Faculty Role
Current
Position
2019 - present Martin Thein
Pediatrics
Resident,
UCSF
Endocrinolog
y Fellow
2019 - present Dana
Greenfield
Pediatrics
Resident,
UCSF
2019 - present Anna
Mrelashvili
Neonatal
Neurology
fellow, UCSF
Career Mentor
Child
Neurologist,
PAMF
2020 - present Daniel Pique
Pediatrics
Resident,
UCSF
Career Mentor
2020 - present Sophia
Karandashova
Pediatrics
Resident,
UCSF
Career Mentor
2020 - present Clare Howard Pediatrics
Resident,
UCSF
2020 - present Matthew
Decker
Pediatrics
Resident,
UCSF
Career Mentor
FACULTY MENTORING
Dates
Name
Position while
Mentored
Mentor Type
Mentoring Role
Current
Position
2013 - present Henry Cheng Assistant
Professor,
Boston
Children's
Career Mentor
2014 - present Mark Petersen Asst
Professor,
UCSF
Career Mentor
2015 - 2020
Larry Shiow
Assistant
Professor,
UCSF
Career Mentor
2016 - present Luke Judge
Asst
Professor,
UCSF
Career MentorPrepared: May 3, 2021
13 of 27
Dates
Name
Position while
Mentored
Mentor Type
Mentoring Role
Current
Position
2020 - present Betsy Crouch Assistant
Professor,
UCSF
Career Mentor
VISITING FACULTY MENTORED
2016 - 2016
Jennifer Muncy
Thomas
UT-Southwestern
2018 - 2018
Jose Martinez
Orgado
Institute of Children and Adolescents (INA) Hospital Clínico
"San Carlos" - IdISSC Profesor Martin Lagos s/n. Madrid,
Spain
2018 - 2018
Joana Grenha Centro Hospitalar de Vila Nova de Gaia/Espinho | CHVNG/E ·
Department of Pediatrics
-
RESEARCH AND CREATIVE ACTIVITIES
RESEARCH AND CREATIVE ACTIVITIES SUMMARY
Research Goals:
The goal of my research is to pursue basic science and translational studies focused on injury
and repair in the full-term neonatal brain. I especially wish to understand how the developing
brain responds to acute, focal injury and mounts protective and regenerative responses, and
methods to enhance these neuroprotective pathways with exogenous therapy. Ultimately, I will
apply these discoveries to design preventive and therapeutic strategies specific to the newborn
brain that will ultimately lower the morbidity and mortality in this vulnerable population.
Summary of Research Accomplishments:
Undergraduate Research and Graduate Medical Training
My prior training and experience have directed me toward, and prepared me to direct, an
independent research program in developing brain injury. As an undergraduate Neuroscience
major, I studied the anesthetic properties of the α-2-adrenergic agonist dexmedetomidine,
under the supervision of Dr. Mervyn Maze at Stanford University. I became comfortable
performing a number of techniques, including intrathecal cannulations and harvesting and
processing the brain and spinal cord in adult rats. My work involved the determination of
effective dosage, synergistic effects and toxicity of dexmedetomidine when used for pain
control. I was able to work with a mentor who guided me through the intricacies of working with
and analyzing results in small animal models, and this resulted in a publication in
Anesthesiology. While in medical school, I followed this experience with a research fellowship
to study wound healing and inflammation under the mentorship of Dr. Jorge Albina in the
Department of Surgery at Brown University. The focus of my project was the characterization
of the anti-infectious activity of wound-derived neutrophils and macrophages, as well as the
respiratory burst activity of neutrophils in rats of different ages.
Post-doctoral trainingPrepared: May 3, 2021
After graduating from the Brown University School of Medicine, I completed residency in
Pediatrics at Harbor-UCLA Medical Center. During rotations in the neonatal intensive care unit
(NICU), I was struck by our limited understanding of disease processes that affect the neonate
and, in particular, limited therapeutic options for a number of common disease processes in
both full-term and preterm infants. During my residency I took advantage of the rich opportunity
at Harbor-UCLA to study injury in the developing lung, specifically bronchopulmonary dysplasia
and possible therapeutic options to prevent its development. I spent parts of my second and
third years of residency working in the lab of Dr. Virender Rehan. I studied the role of
Rosiglitazone, a peroxisome proliferator activated receptor (PPAR) ligand, in preventing
hyperoxia-induced alveolar lung injury in a ventilated neonatal rat model. It is hypothesized that
a PPAR-γ ligand can attenuate hyperoxic lung injury by preventing the transdifferentiation of
lipofibroblasts to myofibroblasts, thereby decreasing the fibrosis associated with chronic lung
disease. My roles included pre-treating 2-week old rat pups with Rosiglitazone or vehicle, and
then anesthetizing and ventilating these rats in room air or 95% O2. In addition, I was involved
with the analysis of lung tissue mRNA and protein expression for type II alveolar cell, lipogenic,
and myogenic markers. This work was presented at WSPR.
Drawn to both this opportunity for inquiry and compelling clinical environment of the NICU, I
decided to pursue training in neonatology and completed a post-doctoral fellowship in
neonatal-perinatal medicine at the University of California, San Francisco (UCSF). I became
interested in bridging my basic science interest in neuroscience with my clinical interest in the
Intensive Care Nursery, and I took the opportunity to do my research in the Neonatal Brain
Disorders Center under the mentorship of Dr. Donna Ferriero. Our initial work focused on the
neuroprotective and neurogenic role of single-dose erythropoietin (EPO) immediately following
neonatal stroke, which demonstrated short-term increases in both brain volume and neuron
number in injured brain tissue. This early work on the effects of single-dose EPO on
histological and cell fate outcomes prompted an evaluation of long-term histological and
cognitive outcomes, which showed that multiple doses of erythropoietin over a one-week
period were most effective in enhancing both long-term histology and cognitive function.
Recent research:
My current research is focused on determining how the full-term brain responds to acute injury
during the neonatal period, and strategies to enhance neuroplasticity and long-term functional
outcomes. My specific research goals are to: (1) clearly define the neuronal subpopulations
that are vulnerable to ischemia and critical for neurodevelopment, (2) determine the
mechanisms of injury and endogenous repair in the immature brain, and (3) define therapeutic
strategies to enhance long-term neurodevelopmental function. Specifically, I am interested in
how the immature brain differs from the adult brain in its response to stroke, and how
reparative mechanisms can be enhanced with delayed therapy. I am currently focused on cell
type-specific changes in the peri-infarct cortex, including alterations in cell fate, function, and
vasculogenesis. In addition, we know that there are individual and sex-based differences in the
response to ischemic injury and exogenous therapies. We are now using Magnetic Resonance
Spectroscopy and advanced imaging techniques to define the metabolomic changes in the
injured deep gray and white matter to determine signatures that can optimize our treatment
strategies and therapeutic options. This will have a significant impact in improving knowledge
and identifying novel therapies to treat early injury. It is my clear desire to apply this type of
translational approach to the field of neonatal brain injury, thereby unifying my interest in
neuroscience and brain development with a goal of improving the care of the newborn. With
this model of early focal brain injury and the ability to examine short and long-term histological
and behavioral outcomes, as well as cell fate outcomes in the core and penumbra of injury, I
am now able to use this model to collaborate with a number of other laboratories at UCSF and
14 of 27Prepared: May 3, 2021
internationally, including the Steven Fancy, Duan Xu, David Rowitch, and Henrik Hagberg labs
to study mechanisms of ischemic brain injury and potential neuroprotective and
neuroregenerative therapies.
My clinical background and research experience has also lead to my participation in clinical
studies of human newborns with encephalopathy and concern for brain injury. For example,
based upon our findings that prolonged EPO treatment (3 doses over 1-week) is most effective
for long-term cognitive/sensorimotor improvement, prolonged treatment regimens were studied
in a Phase 1 trial in full-term newborns with neonatal encephalopathy and concern for
moderate brain injury, the Neonatal Erythropoietin in Asphyxiated Newborns trial (NEAT, PI:
Yvonne Wu). I played an important role in the planning and execution of this trial, examining
safety and pharmacokinetics of moderate to high-dose erythropoietin combined with
hypothermia treatment for neonatal encephalopathy. I continued to play a significant role in the
phase II NEATO feasibility and outcomes trial, and am now serving as a site PI and Executive
Committee/CCC member of the Phase III HEAL trial (Hypothermia + EPO for Neonatal
Encephalopathy). As outlined in the next section, my research program is focused on
mechanisms of regeneration and repair with delayed exogenous therapy for neonatal stroke,
with the ultimate goal of designing better strategies to both protect and repair the newborn
brain.
Importance of the problem: Neonatal stroke constitutes a major health problem in the United
States and worldwide, with rates that continue to increase. The risk of stroke in infants is
greatest within the perinatal period (the weeks immediately prior, and after birth) and is one of
the top 10 causes of mortality in children. Current estimates show an incidence of
approximately 1 in 1900 live births. The causes of perinatal stroke are multifactorial, and the
majority of survivors deal with devastating, life-long neurological compromise that includes
epilepsy, cerebral palsy, or other motor or cognitive disabilities. There are no accepted
therapeutic interventions for the transient ischemia-reperfusion that is the most common cause
of early stroke, and the mechanisms of repair have not been elucidated. In addition, stroke is
frequently not diagnosed in the acute period, making identification of late treatment alternatives
crucial. New post-stroke strategies are therefore necessary to diminish cellular damage and
death while also providing new pathways to recover tissue over a prolonged period of time.
Current and Proposed Research:
Differences exist between adults and neonates in the response to brain injury, including timing
of and susceptibility to excitotoxicity, inflammation, oxidative stress, and apoptosis. These, in
turn, have a significant impact on the neurovascular niche through angiogenesis, neural
precursor cell proliferation and fate. Ischemia-reperfusion injury is the most common cause of
perinatal stroke and manifests as an ischemic core with necrotic cell death, surrounded by a
vulnerable peri-infarct region. Within this region, angiogenesis and neuronal repopulation occur
in close proximity, facilitating mutually supportive neuron-endothelial cell interactions. Blood
vessels serve as a scaffold for neuronal migration in response to injury, but may also have a
significant paracrine effect via growth factor release and secondary signaling pathway
activation that leads to repair. Modulating this neurovascular niche may be a potential target for
ischemic brain injury, especially in the developing brain, where deficits in survivors can be
devastating and have a substantial socioeconomic impact.
In recent years cell-based therapies have emerged as a potential treatment for various CNS
diseases. Our group and others have shown that mesenchymal stem cells (MSC) given after
neonatal stroke in the rodent reduce lesion volume and improve motor function. These
improved outcomes occur even in the absence of survival of engrafted cells, suggesting
15 of 27Prepared: May 3, 2021
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transplanted cells may induce repair by stimulating secretion of growth and differentiation
factors that provide an environment to enhance repair. We have shown that delayed
administration of MSC is beneficial to functional and histological outcome following stroke, but
genetic modification to enhance brain-derived neurotrophic factor (BDNF) secretion had no
additional benefit. It is possible that other factors that have specific effects on the
neurovascular unit, such as erythropoietin (EPO), may provide additional benefit.
Our goal is to determine the mechanism of regeneration and repair with delayed exogenous
therapy for neonatal stroke by focusing on the vascular response, in relationship to changes in
neuronal cell fate. Our primary hypothesis is that MSC pretreated with EPO will promote
vascular growth and remodeling and increase neurogenesis following early ischemia
reperfusion injury, leading to long-term histological and functional improvement. This approach
is unique because it focuses on the effects on the neurovasculature, which we hypothesize is
important in the repair process, and it will combine two desirable interventions that have shown
promise into one treatment modality that may widen the therapeutic window for a disease
process where diagnosis is often delayed. We are also investigating the cell-type specific
mechanisms of programmed cell death that occur at later time points after ischemic injury and
delayed treatment, focusing on necroptosis and ferroptosis in the injured penumbra.
There are differences in how individual neonates respond to early brain injury and therapeutic
hypothermia, which currently represents the standard of care for neonates exposed to perinatal
hypoxia/ischemia. There are also no good biomarkers for either severity of injury or the
potential to respond to therapy. Changes in intracellular "metabolic fingerprints", or
metabolomics, can identify tissues at risk for continued energy failure and injury. Recent
studies in nonhuman primates show a particular metabolic profile in blood during the transition
from intrauterine to extrauterine life. Cerebral proton magnetic resonance signatures can
differentiate between control and mice suffering from ischemic injuries, and hyperpolarized
carbon-13 (HP-13C) demonstrates dynamic metabolic conversion changes over the early
lifespan as well as over the course of ischemic injuries. These suggest that even more precise
information can be derived from brain using MR spectroscopic methods. By quantifying brain
intracellular metabolites relevant to energy metabolism (PCr), osmolytes (myo-inositol), and
neuron integrity (N-Acetyl-Aspartate) through proton MRS and dynamic metabolic conversion
from pyruvate to lactate using HP-13C MRI, we can characterize correlations among individual
metabolic fingerprints and outcome, permitting a unique and novel determination of the
suitability of the neonate for specific therapeutic strategies.
We hypothesize that after a focal ischemic insult, the structural and metabolic fingerprint of the
tissue will show distinct patterns that are indicative of degree of injury and have predicative
value in terms of indicating outcome. Identification of altered metabolic fingerprints will allow for
better selection of neonates who might respond to/benefit from adjunctive therapy with
erythropoietin. The proton MRS will provide steady state metabolic information while the HP-
13C MRI will offer insights to real-time changes in metabolic conversion. This work will not only
move the field forward in regard to understanding mechanisms, but present a novel and unique
method to provide translatable therapy to newborns with stroke.
RESEARCH AWARDS - CURRENT
1. 1U01NS092764-01
site-PI
1.8 calendar
months, 15 %
effort
Wu, Juul (PI)
NINDS
09/01/2016
08/31/2021Prepared: May 3, 2021
17 of 27
High-dose Erythropoietin for Asphyxia and
Encephalopathy Study (HEAL study)
$ 1,812,889
direct/yr 1
$ 10,000,000 total
To determine if High-dose erythropoietin reduces the composite outcome of death or long
term neurodevelopmental impairment in term infants with hypoxic-ischemic encephalopathy.
Site-PI, Executive Committee/CCC member
2. 1R35NS097299-01
co-investigator
1.8 calendar
months, 15 %
effort
Ferriero (PI)
NINDS
12/01/2016
11/30/2023
Precision therapy for neonatal brain injury
$ 715,821
direct/yr 1
Lack of oxygen to the newborn brain is the major cause of lifelong disability in children
resulting in mental retardation, epilepsy and cerebral palsy. Understanding pathways for
protecting the brain will result in therapeutic avenues for brain recovery.
3. 1 R01 NS107039-01
PI
4 calendar
months, 30 %
effort
Gonzalez (PI)
NINDS
12/15/2017
11/30/2022
Enhanced cellular therapy for neonatal stroke
$ 250,000
direct/yr 1
$ 1,000,000 total
The goal of this project is to determine the mechanisms of regeneration and repair with
delayed cellular therapy for neonatal stroke by focusing on the vascular response to brain
injury. This will study the effects of mesenchymal stem cells pre-treated with erythropoietin on
long-term outcomes.
PI
RESEARCH AWARDS - SUBMITTED
1. R01HD099179
co-PI
20 % effort
Gonzalez, Xu (PI)
NIH/NINDS
04/01/2021
03/31/2026
Quantifying Dynamic Metabolism in the Neonatal
Stroke Model
$ 2,490,625.00 total
Neonatal stroke constitutes a major health problem worldwide, with rates that continue to
increase. Changes in intracellular "metabolic fingerprints", or metabolomics, can identify
tissues at risk for continued energy failure and injury. We will us in vivo 1H and
hyperpolarized C-13 to identify altered metabolic fingerprints to select neonates who may
respond to or benefit from therapy after ischemic injury. Previous score: 45
2. NIH UG3/UH3
Site-PI
5 % effort
Chalak (PI)
NIH/NINDS
04/01/2021
03/31/2026
CCOOL PRIME (Cooling Comparative
Effectiveness Prospective Study in Infants with
Mild Encephalopathy)Prepared: May 3, 2021
18 of 27
We will perform a comparative effectiveness evaluation of cooling for mild HIE within a
prospective cohort of infants at 11 academic centers whose practices are mixed for either
therapeutic hypothermia or supportive care. The central aim is to determine in infants meeting
predefined criteria for mild HIE if there are differences in the primary outcome of Bayley IV at
2 years based on the use of cooling or supportive care. The UG3 will be used for operational
planning registry, finalize regulatory approval, and train personnel at sites. During UH3
(implementation) 460 infants will be recruited follow-up at 22-26 months.
RESEARCH AWARDS - PAST
1. R01 NS033997
co-investigator
1 calendar month
% effort
Ferriero (PI)
NIH/NINDS
04/01/1996
01/31/2017
Oxidant mechanisms in neonatal brain injury
The goal of this grant study is to understand how the exact timing and control of paracrine
signaling is essential for translation of EPO dosing in the clinic.
2. P50 NS35902
co-investigator
Ferriero (PI)
NINDS
04/01/1997
01/31/2013
Mechanisms of Ischemic Neonatal Brain Injury
The goal of this project is to investigate the role of ischemia in the generation of neonatal
brain injury. Project 2 focuses on the role of fructose bis-phosphate, and Project 3 on growth
factors after hypoxic-ischemic injury.
3. Thrasher
co-investigator
Wu (PI)
Thrasher Foundation
08/01/2008
12/31/2012
Phase I multicenter clinical trial of early high-dose
erythropoietin in term infants with hypoxic-ischemic
encephalopathy
The Neonatal Erythropoietin in Asphyxiated Term Infants Trial (NEAT trial) As a participating
center in this phase I trial of high-dose erythropoietin (EPO) therapy, we will be recruiting
and enrolling newborn infants with hypoxic-ischemic encephalopathy. We will be responsible
for identifying potential patients, obtaining consent, giving the study drug and monitoring for
side effects, and communicating our data to the Coordinating Center (UCSF).
4. 1K08NS064094-01A3
PI
Gonzalez (PI)
NIH/NINDS
4/1/2011
3/31/2016
Erythropoietin and Neurogenesis after Neonatal
StrokePrepared: May 3, 2021
19 of 27
Study: Stroke is a major cause of neonatal morbidity and mortality, and the immature brain
responds differently to injury with enhanced plasticity. The goals are to clearly define the
neural stem cell population responsible for early development and repair after neonatal
stroke, and to determine the mechanisms and timing of exogenous erythropoietin enhanced
repair in the developing brain.
5. RAP
PI
Gonzalez (PI)
UCSF Academic Senate
01/01/2012
12/31/2014
Effects of neonatal stroke and erythropoietin on cell
fate and neurogenesis
6. Thrasher
co-investigator
Wu (PI)
Thrasher Research Fund
08/01/2013
07/30/2016
Neonatal Erythropoietin and Therapeutic
Hypothermia Outcomes in Newborn Brain Injury
(NEAT O)
Study: Hypoxic-ischemic encephalopathy (HIE), a condition of reduced blood and oxygen
flow to a baby's brain near the time of birth, may cause death or neurologic disability.
Cooling therapy (hypothermia) provides some protection, but about half of affected infants
still have a poor outcome. This clinical trial will determine if the drug erythropoietin, given
with hypothermia, is safe to use as a treatment that may further reduce the risk of neurologic
deficits after HIE.
7. Harrington
co-PI
Rowitch (PI)
Harrington Discovery Institute
4/1/2014
3/31/2016
Sonic hedgehog agonist (SAG) neuroprotection for
neonatal brain injury
Study: No drugs are currently available to prevent neurological complications of preterm
birth or stroke. This study will test a novel therapeutic approach using a small-molecule
agonist of the Sonic Hedgehog (SHH) pathway, called “SAG.” We have shown SAG can
prevent certain kinds of neonatal brain injury in small animal models. This study will test
safety and efficacy of SAG in additional mouse and rat models of newborn brain injury. We
will determine both the structural and mechanistic basis of SAG effects against these
injuries.
8. P01 NS082330
Co-investigator
1.2 calendar
month, 10 % effort
Ferriero (PI)
NIH/NINDS
01/01/2014
12/31/2018
Repair after Neonatal Brain InjuryPrepared: May 3, 2021
20 of 27
This grant proposes to study both structural and functional correlates of brain developmental
maturation and network organization using advanced imaging techniques in our human
populations and similar correlates in newborn rodents with a focus on defining basic
mechanisms of repair. We will translate these findings to the development of appropriate
hardware and software for imaging the fragile newborn to enhance our capabilities in
understanding how and when reparative processes originate and are executed.
9. REAC
PI
Gonzalez (PI)
UCSF
01/01/2015
06/30/2016
The Role of Erythropoietin in Enhancing Synaptic
Plasticity and Neural Circuit Formation after
Neonatal Stroke
$ 30000 direct/yr 1 $ 30000 total
10. Omniox
PI
Gonzalez (PI)
Omniox
7/01/2015
06/30/2016
Efficacy of OMX-4.80-MP in neonatal stroke
$ 10000 direct/yr 1 $ 10000 total
Omniox has previously demonstrated that OMX-4.80-MP oxygenates hypoxic tissue and
accumulates in infarcted areas. Furthermore, OMX-4.80MP when given post infarction can
reduce infarct volume and ameliorate short and long-term impairments of the sensorimotor
functions in multiple adult stroke models. The overall objective of the present study is to
extend these findings in neonatal stroke model and test the efficacy of OMX-4.80-MP in
reducing brain infarct volume in neonatal stroke.
11.
co-PI
as needed, 0 %
effort
Ferriero (PI)
Anida Pharma, Inc.
07/01/2016
06/30/2018
NPD1 for neonatal brain injury
$ 40,694 total
To evaluate the efficacy of multiple doses of NPD1 in treating neonatal rodent stroke. This
study is focused on short-term histological outcomes, comparing different dosing regimens.
Neonatal stroke model, determination of outcomes
12. RAS A127552
PI
as needed % effort Gonzalez (PI)
NIH-NCATS
06/01/2018
05/30/2019
Quantifying Metabolic Changes in the Newborn
Brain Following Stroke
$ 40000 direct/yr 1 $ 40000 total
Our goals are to evaluate the structural and metabolic fingerprints of the tissue following
focal ischemic injury, which will show distinct patterns that are indicative of degree of injury
and predictive in terms of indicating outcome. Identification of altered metabolic fingerprints
will allow for better selection of neonates who might respond to/benefit from different
therapeutic strategies. This will present a novel and unique method to provide translatable
therapy to newborns with stroke.
PIPrepared: May 3, 2021
PEER REVIEWED PUBLICATIONS
1. Guo TZ, Reid K, Davies MF, Nacif-Coelho C, Rabin BC, Gonzalez F, Maze M. Chronic
desipramine treatment desensitizes the rat to anesthetic and antinociceptive effects of the
alpha2-adrenergic agonist dexmedetomidine. Anesthesiology. 1998 Jun; 88(6):1634-42.
PMID: 9637658
2. Gonzalez FF, Miller SP. Does perinatal asphyxia impair cognitive function without cerebral
palsy? Arch Dis Child Fetal Neonatal Ed. 2006 Nov; 91(6):F454-9. PMID: 17056843.
PMCID: PMC2672766
3. Gonzalez FF, McQuillen P, Mu D, Chang Y, Wendland M, Vexler Z, Ferriero DM.
Erythropoietin enhances long-term neuroprotection and neurogenesis in neonatal stroke.
Dev Neurosci. 2007; 29(4-5):321-30. PMID: 17762200
4. Gonzalez FF, Ferriero DM. Therapeutics for neonatal brain injury. Pharmacol Ther. 2008
Oct; 120(1):43-53. PMID: 18718848
5. Gonzalez FF, Abel R, Almli CR, Mu D, Wendland M, Ferriero DM. Erythropoietin sustains
cognitive function and brain volume after neonatal stroke. Dev Neurosci. 2009; 31(5):403-
11. PMID: 19672069. PMCID: PMC2820334
6. Gonzalez FF, Ferriero DM. Neuroprotection in the newborn infant. Clin Perinatol. 2009
Dec; 36(4):859-80, vii. PMID: 19944839. PMCID: PMC2786822
7. Spadafora R, Gonzalez FF, Derugin N, Wendland M, Ferriero D, McQuillen P. Altered fate
of subventricular zone progenitor cells and reduced neurogenesis following neonatal
stroke. Dev Neurosci. 2010 Jul; 32(2):101-13. PMID: 20453463
8. Wang H, Tang J, Xiong Y, Li X, Gonzalez F, Mu D. Neonatal community-acquired
pneumonia: pathogens and treatment. J Paediatr Child Health. 2010 Nov; 46(11):668-72.
PMID: 20796185
9. Gonzalez FF, Fang A, Ferriero DM. Is erythropoietin the answer? Pediatr Res. 2011 Jan;
69(1):2-3. PMID: 21150548
10. Zhao J, Gonzalez F, Mu D. Apnea of prematurity: from cause to treatment. European
Journal of Pedaitrics. 2011; 170(9):1097-105. PMID: 21301866
11. Xiong T, Gonzalez F, Mu DZ. An overview of risk factors for poor neurodevelopmental
outcome associated with prematurity. World J Pediatr. 2012 Nov; 8(4):293-300. PMID:
23151855
12. Wu YW, Bauer LA, Ballard RA, Ferriero DM, Glidden DV, Mayock DE, Chang T, Durand
DJ, Song D, Bonifacio SL, Gonzalez FF, Glass HC, Juul SE. Erythropoietin for
neuroprotection in neonatal encephalopathy: safety and pharmacokinetics. Pediatrics.
2012 Oct; 130(4):683-91. PMID: 23008465. PMCID: PMC3457622
13. Fang AY, Gonzalez FF, Sheldon RA, Ferriero DM. Effects of combination therapy using
hypothermia and erythropoietin in a rat model of neonatal hypoxia-ischemia. Pediatr Res.
2013 Jan; 73(1):12-7. PMID: 23085817. PMCID: PMC3540182
14. Gonzalez FF, Larpthaveesarp A, McQuillen P, Derugin N, Wendland M, Spadafora R,
Ferriero DM. Erythropoietin increases neurogenesis and oligodendrogliosis of
subventricular zone precursor cells after neonatal stroke. Stroke. 2013 Mar; 44(3):753-8.
PMID: 23391775. PMCID: PMC3689426
21 of 27Prepared: May 3, 2021
15. van Velthoven C*, Gonzalez F*, Vexler Z, Ferriero D. Stem cells for neonatal stroke-the
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| 日期 | 时间 | 会场 | Session | 角色 | 讲题 |
|---|---|---|---|---|---|
| 2021-12-12 | 14:40-15:00 | 新生儿专场 Neonatology |
新生儿专场 下午 Neonatology(p.m.) |
讲者 Speaker | 足月儿脑损伤的治疗策略Delayed Treatment Strategies for Full-Term Brain Injury |
| 2021-12-12 | 15:40-15:55 | 新生儿专场 Neonatology |
新生儿专场 下午 Neonatology(p.m.) |
讨论 Discussant | 讨论Discussion |
美迪康会务通