Nicole A.

Sierra

nsierra9652@sdsu.edu
832-490-6221

EDUCATION

San Diego State University

Chemistry- emphasis Biochemistry Major
Anticipated Graduation: May 2024

LICENSURES

IV Sterile Compounding and Aseptic Technique: Lone Star College -Tomball Pharmacy Technology Program 2020

HONORS AND AWARDS

Nyewa Presidential Leadership Program Scholarship 2020-2021

SDSU SSF Emergency Funding Recipient 2021
SDSU NIH IMSD Scholar 2021-2022
SDSU Student Research Symposium Provost's Award 2021
SDSU NIH MARC Scholar 2022-2024
ABRCMS Certificate of Achievement- Presentation Award 2023

RESEARCH EXPERIENCE

IMSD Undergraduate Research Scholar Fall 2020 - Fall 2021

Department of Civil, Constructional, and Environmental Engineering
Lab of Dr. Alicia Kinoshita
San Diego State University
San Diego, CA

Studying certain water parameters along the coast of the Amazon River basins, to investigate the
correlation between wildfires and effects of water quality. By analyzing water quality data available at
the varying Brazilian National Water Resource Information System (SNIRH) stations, primarily
focussing on turbidity, total suspended solids (TSS), total organic carbon (TOC), and pH. Studying
stream gauges and the precipitation and investigating which areas contribute the most to the overall
runoff and the total runoff. Including the design of charts and tables from data. Part of a member of 3
personal teams with a graduate student in another undergraduate student presenting findings at the
2021 San Diego State Student Research Symposium
Supervisor/Mentor: Dr. Alicia M. Kinoshita

Undergraduate Biochemistry Summer Research Intern Summer 2022

Infectious Diseases and Vaccines Therapeutic Area
Janssen BioPharma- Johnson & Johnson
South San Francisco, CA

The internship consisted of joining Janssen Biopharma, Inc., a member of Johnson’s Family of
Companies, as a summer research internship position in the Viral Biochemistry group in the
Infectious diseases and Vaccines Therapeutic area. The study was the development of therapeutic
drugs for a broad range of infectious diseases including Rhinovirus, RSV, Influenza, HIV, and
Hepatitis B. I supported active research discovery projects and performed relevant biochemical and in
vitro assay development to assess functional outcomes. The responsibilities conducted were to
express, purify, and characterize proteins from bacterial and insect cell cultures to support
biochemical assay development for compound profiling and High Throughput Screening (HTS).
Perform biophysical/biochemical assays including analytical size-exclusion chromatography,
AlphaLISA, time-resolved FRET, and radiometric enzymatic assays. I further, interpreted,
summarized, and presented the findings of the research during internal and site-wide team meetings.
Supervisor/Mentor: Dr.Arthur Hauenstein

IMSD/MARC Undergraduate Research Scholar Fall 2021- Present

Department of Chemistry and Biochemistry
Lab of Dr. Christal Sohl
San Diego State University
San Diego, CA

The study of how changes in enzymes occur in health and disease, by using kinetics and IDH1
mutations that occur in gliomas. Studying how IDH1 mutations can be oncogenic and tumor
suppressors within enzymes. As the work continues, we study the changes that occur in the tumor
microenvironment when regulating the activity of wild-type IDH1. These mutations change enzyme
functions which provide a crucial role in the understanding of cancer. I have been able to understand
how altered IDH1 mutation activity leads to increased levels of D-2-hydroxyglutarate, D2HG, and an
oncometabolite in gliomas.
Supervisor/Mentor: Dr. Christal Sohl
ABSTRACTS

M Peters, N Sierra, S Jorge. Impacts of Wildfires on Coastal Discharges in the Amazon

River Basin, Fourteenth Annual Student Research Symposium of the division research
and innovation at San Diego State University, San Diego, CA, 2021.
M Peters, N Sierra, S Jorge. Impacts of Wildfires on Coastal Discharges in the Amazon
River Basin, SACNAS Society for Advancement of Chicanos/Hispanics and Native
Americans in Science, virtual presentation, 2021.

The vulnerability of coastal areas to terrestrial watershed disturbances, such as wildfires, remains
unknown and unquantified. In 2020 alone, there was an unprecedented amount of wildfires,
causing damage and disruption throughout the world, with Australia experiencing its largest
bushfire in history and the Amazon continuing to battle unusually high numbers of fires. As
many coastal waterways are downstream of terrestrial areas that are susceptible to wildfires, it is
critical to evaluate the impacts of wildfires on vulnerable marine environments. This study sets
out to identify and quantify the impacts of wildfires on coastal regions. Large spatial datasets are
utilized to interlink spatial and temporal dynamics of terrestrial processes and disruptions from
wildfires with coastal runoff and ecosystem shifts in the Amazon River Basin. This work will
focus specifically on the area within the Brazilian state of Roraima where a large number of fires
have been observed in recent years upstream of the coast. The extent and magnitude of previous
wildfires were characterized using satellite-based products, Enhanced Vegetation Index (EVI),
Normalized differential vegetation index (NDVI), and differenced normalized burn ratio
(dNBR), to compare pre-and post-fire biomass and estimate the burn severity of plant material
and soil. Discharge flows and water quality data were obtained from multiple data repositories
available through the Brazilian government, with the majority of the river gauge stations being
actively managed by the Geological Survey of Brazil (GSB). This data was compiled for fires
that occurred between 2010 to 2020 to evaluate post-fire water quality response. A subset of fires
concentrated along the Branco River and Rio Negro, two large tributaries to the Amazon River,
was examined in further detail to identify trends in water-quality response. Assembling this
extensive dataset provided the unique opportunity to determine the most common post-fire water
quality changes in the Branco River, Rio Negro, and Amazon River. Results from this study will
further be used to identify shifts in water quality and impacts of the coastal discharge of the
Amazon River post-fires.

N Sierra, E Albekioni, K Sabo, Christal Sohl. Exploring the mechanisms of IDH1 pH

sensitivity, Fifteenth Annual Student Research Symposium of the division research and
innovation at San Diego State University, San Diego, CA, 2022.
N Sierra, E Albekioni, K Sabo, Christal Sohl. Exploring the mechanisms of IDH1 pH
sensitivity, SACNAS Society for Advancement of Chicanos/Hispanics and Native
Americans in Science at San Juan, Puerto Rico, 2022.

Globally, cancer patients are significantly impacted by the proto-oncogene isocitrate

dehydrogenase 1 (IDH1). While many cancers are driven by mutations in IDH1, resulting in the
catalysis of a new reaction that has been shown to drive tumor formation, wild-type (WT) IDH1
has also been shown to drive many cancer types. WT IDH1 drives the oxidative decarboxylation
reaction of isocitrate to alpha-ketoglutarate, with concomitant conversion of NADP+ to ​NADPH.
This reaction can support tumor growth by synthesizing alpha keto-glutarate. We know from
previous structural informatics and pKa calculations that the residue D273 in IDH1 is sensitive to
changes in pH, allowing IDH1 to serve as a pH sensor. By affecting the activity of pH sensors,
cellular pH can regulate protein-protein and protein-ligand interactions, including the stability
and activity of a protein. D273 is located in the first third of the α10 helix, an essential regulatory
domain. To determine the role of D273 in pH sensitivity, experimental mutants were designed to
have minimal disruption in the overall structure but still destroy the ability of the residue to
ionize. The mutants produced very drastic decreases in catalytic efficiency for the forward
reaction as compared with WT IDH1. Here we describe the pH sensitivity of a new ionizable
mutant, D273E IDH1. Using site-directed mutagenesis, the formation of the D273E mutant was
made and the enzyme was heterogeneously expressed and purified. We predict this mutant will
retain pH sensitivity when measuring the rates of αKG production since it can change its
ionization state.

N Sierra, E Albekioni, Nalani Coleman, Rachel Khoury, An Hoang, Christal Sohl.

R132Q IDH1 sensitivity to reducing agents, Sixteenth Annual Student Research
Symposium of the division research and innovation at San Diego State University, San
 Diego, CA, 2023. N Sierra, E Albekioni, Nalani Coleman, Rachel Khoury, An Hoang,
Christal Sohl. R132Q IDH1 sensitivity to reducing agents, ABRCMS (Annual
Biomedical research conference for minoritized scientists) at Phoneix, AZ,2023.

The proto-oncogene IDH1, isocitrate dehydrogenase 1, is a gene that provides enzymes the
ability to break down fats for energy and protect cells. In the normal wild-type oxidative
decarboxylation reaction, isocitrate produces alpha-ketoglutarate, with the reactant NADP+
being converted to ​NADPH. However, mutant IDH1 can catalyze a neomorphic reduction, the
NADPH-dependent reduction of alpha-ketoglutarate to D-2-hydroxyglutarate, D2HG, which can
competitively inhibit alpha ketoglutarate-dependent enzymes. We hope to investigate the
catalytic efficiency of the enzyme to discover the relationship between kinetics and tumor
phenotypes. We have previously shown that the mutation R132Q produces high levels of D2HG
while still being able to produce alpha-ketoglutarate, unlike other mutants. Furthermore, we
previously solved a crystal structure of R132Q with the mutant bound to isocitrate and NADP+
substrates under reducing conditions to stimulate the cellular environment. This crystal structure
led to the discovery of the reducing agent, TCEP, forming an adduct with NADP+. The impact of
this adduct on the catalytic activity of the mutant R132Q IDH1 is unknown. We hypothesize that
the NADP+-dependent normal reaction will be inhibited due to the unavailability of the NADP+
substrate. We have conducted steady-state kinetic assays on R132Q mutant at varying
concentrations of reducing agents to determine the impact of the TCEP-NADP adduct on R132Q
catalysis. We show that observed rates of R132Q decrease as reducing agent concentrations
increase, with different reducing agents having unique tendencies for inhibition. This project can
reveal possible precautions for researchers to be aware of when crystallizing IDH1 and
performing catalytic reactions, as well as help us clarify mechanisms of catalysis.

MEDICAL-RELATED EXPERIENCE

Intern Pharmacy Technician 2019-2020

Walgreens Pharmacy
Katy, TX

Assisted with receiving and verifying prescriptions, including preparing and filing the
medication with accuracy. Assisted with insurance claims and ensured the availability of
drugs. Maintained inventory and assist the pharmacy team with phone calls and customer
service.
Supervisor: Lorraine Istre, MD

CONFERENCES ATTENDED
SDSU Student Research Symposium 2021
SDSU Undergraduate Research Symposium 2021
SACNAS (Society for the Advancement of Chicanos/Hispanics and Native Americans in Science) 2021
SDSU Student Research Symposium 2022
SDSU Undergraduate Research Symposium 2022
SACNAS (Society for the Advancement of Chicanos/Hispanics and Native Americans in Science) 2022
SDSU Student Research Symposium 2023
SDSU Undergraduate Research Symposium 2023
ABRCMS (Annual Biomedical research conference for minoritized scientists) 2023
SDSU Student Research Symposium 2024

LANGUAGES

English (Native), Spanish (Fluent)

REFERENCES

Cathie Atkins, Ph.D. MARC Program Principal Investigator/ Director

Principal Investigator/ Director
College of Sciences-GMCS 604
San Diego State University
5500 Campanile Drive
San Diego, CA 92182-1010
(619) 594-5350
catkins@sdsu.edu

Christal Sohl, Ph.D. Associate/Principal Investigator

Professor/Supervisor
Department of Chemistry and Biochemistry
College of Sciences- CSL 328
San Diego State University
5500 Campanile Drive
San Diego, CA 92182
(619) 594-2053
csohl@sdsu.edu
Alicia M. Kinoshita, Ph.D. Associate/Principal Investigator
Professor/Supervisor
Department of Civil, Constructional, Environmental Engineering
College of Engineering 424, office E421-F
San Diego State University
5500 Campanile Drive
San Diego, CA 992182-1324
(619) 594-1330
akinoshita@sdsu.edu

Arthur Hauenstein, Ph.D. Senior Scientist/Janssen Infectious Disease

Senior Scientist, Biochemistry
Janssen BioPharma - Pharmaceuticals Companies of Johnson & Johnson
1600 Sierra Point Pkwy, Brisbane, CA
South San Francisco, CA 94005
(650) 763-5627
ahauenst@its.jnj.com

Antonett Madriaga Senior Associate Scientist/Janssen Infectious Disease

Senior Associate Scientist, Biochemistry
Janssen BioPharma - Pharmaceuticals Companies of Johnson & Johnson
1600 Sierra Point Pkwy, Brisbane, CA
South San Francisco, CA 94005
(708) 288-9722
AMadriag@its.jnj.com

Thelma C. Chavez MARC program Coordinator

Coordinator/Mentor
Center for the Advancement of Students in Academia
College of Sciences- GMCS 322B
San Diego State University
5500 Campanile Drive
San Diego, CA 92182-1016
(619) 594-7195
thelma.chavez@sdsu.edu
Michelle Altemus IMSD Program Coordinator
Coordinator/Mentor
Center for the Advancement of Students in Academia
College of Sciences- GMCS 322B
San Diego State University
5500 Campanile Drive
San Diego, CA 92182-1016
(619) 594-3744
maltemus@sdsu.edu

Maureen Paolini Mentor

Mentor
San Diego State University
5500 Campanile Drive
San Diego, CA 992182-1324
(619) 200- 4940
mpaolini@sdsu.edu

Michelle Peters Graduate Student/Mentor

Department of Civil, Constructional, Environmental Engineering
San Diego State University
5500 Campanile Drive
San Diego, CA 992182-1324
(702) 606-8742
michellehpo@gmail.com

Elene Albekioni Graduate Student/Mentor

Department of Chemistry/Biochemistry
College of Sciences- CSL 328
San Diego State University
5500 Campanile Drive
San Diego, CA 92182
(619) 594-2053
ealbekioni2@sdsu.edu