Alberti Lab

We are a diverse and inclusive group of scientists cooperatively working to understand the role of mutant splicing factors in myeloid blood cancers in order to identify molecular vulnerabilities to therapeutically exploit and improve patient’s lives.

Our Research:

Large-scale DNA sequencing efforts from the past decade have successfully identified genes that are recurrently mutated in clonal myeloid malignancies (myelodysplastic syndromes [MDS], myeloproliferative neoplasms [MPN], and acute myeloid leukemia [AML]) and age-related clonal hematopoiesis (CH). Notably, these genes cluster into specific functional pathways, such as mRNA splicing, chromatin modification (e.g., ASXL1, BCOR, TET2), transcription, and signal transduction. The highly recurrent missense mutations in splicing factor (SF) genes (e.g., U2AF1, SRSF2, SF3B1) are usually associated with dysplastic morphologic features and found in >50% of patients with MDS or MDS/MPN and those who have developed secondary AML (sAML). SF mutations are typically identified in the founding clone of MDS patients, implicating dysregulation of RNA splicing as an important driver of disease. Although each of these SFs are integral to 3’-splice site recognition during splicing, each mutant leads to distinct aberrant splicing patterns in patients. Whether SF mutants converge on dysregulating a common molecular program through aberrant splicing or induce MDS through non-canonical mechanisms is still unknown. Most patients harbor additional genetic abnormalities, and the positive or negative enrichment of specific mutation pairs suggests cooperative or deleterious functional interactions between them. Most importantly, it is still fundamentally unclear how or why SF mutations gain clonal dominance in myeloid malignancies. Collectively, we hope to better understand the genetic and molecular basis of SF mutations in the initiation, development, and progression of CH and malignancy, and identify molecular liabilities to therapeutically target. In this regard, the lab is pursuing the following novel directions by employing a combination of novel genetically engineered mouse models and patient-derived samples in conjunction with high-throughput genomic approaches. Mutations in the U2AF1 gene provide an ideal model for these studies as they occur at one of two hotspot codons (S34 and Q157), and they are each associated with different clinical features, outcomes, alternative splicing, and co-occurring gene mutations in patients (Alberti et al, in preparation)

  • Differential effects of mutant U2AF1-S34F and U2AF1-Q157R in hematopoietic diseases.
  • Role of epigenetic dysregulation in SF mutant myeloid malignancies.
  • Effects of aging and stress in selection of SF mutations in clonal hematopoiesis.

 

The Team:

  • Michael O. Alberti, M.D., Ph.D. (Principal Investigator)
  • Brittany LeBere (Lab Manager)
  • Claire Ryan, M.Sc. (Research Professional)
  • Thomas Salvetti (Research Professional)
  • Bridget Hoag (CANB Graduate Student, Co-Mentored with Dr. James DeGregori [Primary])
  • Holly Shankle (Gates Summer Internship Program, Summer 2024)

The Alberti Lab is actively recruiting motivated and enthusiastic postdocs, graduate students, technicians, and part-time undergraduate students to work and assist on projects related to hematopoietic stem cells, alternative splicing, epigenetics, and blood cancer research! Please send a cover letter, CV (or resume), references, and research statements (for postdocs) to Dr. Alberti.

 

The lab also participates in the Cancer Research Experience for Undergraduates (CREU) and Gates Summer Internship Program (GSIP).

 

Lab Alumni:

  • Ilana Baum (Gates Summer Internship Program, Summer 2023)
  • Brandon Figueroa (High School Student, Summer 2023)
  • Perpetual Kyei (CANB Graduate Program Rotation Student, Fall 2023)

Publications:

 

The Alberti Lab is committed to sharing our discoveries and contributions to blood cancer research with the scientific and lay communities in a timely and accessible manner. As such, we plan to support the following innovative publishing models as much as possible: bioRxiv, Review Commons, Life Science Alliance, and eLife. Full bibliography is available at MyNCBI. Selected references are below:


Current Funding:

 

Lab Contact Info:

 

12801 E 17th Ave | RC-1 South, L18-5401K | Aurora, CO 80045 | United States

 

303-724-2934 | Twitter


Alberti_Michael_2022_web

Michael Alberti MD, PhD

Assistant Professor - Molecular Pathology
  • Pathology (SOM)
  • University of Colorado, Anschutz
  • Department of Pathology

Email Address:michael.alberti@cuanschutz.edu

Mailing Address:
  • CU Anschutz

Research I South

12801 East 17th Avenue

8104

L18-5114

Aurora, CO 80045

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As a physician-scientist I am interested in understanding the genetic and molecular basis of splicing factor gene mutations in clonal hematopoiesis and myeloid malignancies, such as myelodysplastic syndromes (MDS). My postdoctoral work demonstrated that mutations in the U2AF1 splicing factor gene provide an ideal model for these studies as they occur at one of two hotspot codons (S34 and Q157) in separate zinc finger domains, and each of these mutations are associated with different clinical features, outcomes, alternative splicing, and co-occurring gene mutations in MDS patients. Complimentary experiments using U2af1(S34F/+) and U2af1(Q157R/+) small animal models support these observations and have also revealed differential activation of several key signaling pathways. The goal of our lab's research program is focused on answering the following questions:

(1) Why are splicing factor mutations highly enriched in clonal myeloid malignancies (e.g., MDS) compared to other types of cancer?

(2) What are the individual and shared mechanisms by which different splicing factor mutations induce MDS?

(3) What are the dynamics facilitating acquisition of additional mutations in the context of splicing factor mutant disease?

Areas of Expertise

Molecular Pathology; Genetics of Myeloid Malignancies

Education, Licensure & Certifications

Education:
BS, Biochemistry & Molecular Biology, California Lutheran University (2005)
PhD, Pathology, University of Alabama at Birmingham (2011)
MD, University of Alabama at Birmingham (2013)

Postdoctoral Education:
Residency, Clinical Pathology, University of California Los Angeles Medical Center (2016)
Fellowship, Molecular Genetic Pathology, Washington University in St. Louis School of Medicine (2017)
Postdoc Fellowship, Washington University in St. Louis School of Medicine (2017-2022)

Licensure:
California Medical License (2015-2016)
Missouri Medical License (2016-2022)
Colorado Medical License (2022-present)

Certifications:
American Board of Pathology, Clinical Pathology (2016)
American Board of Pathology, Molecular Genetic Pathology (2017)

Awards

Barry M. Goldwater Foundation Scholar (2004)
Glenn T. Seaborg Science Award, Swedish Council of America (2005)
William Boyd Medal for Excellence in Pathology, Alabama Association of Pathologists and UAB Department of Pathology (2013)
Paul E. Strandjord Young Investigator Award, Academy of Clinical Laboratory Physicians and Scientists (2015)
Career Development Award, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA (2015-2016)
Paul Calabresi K12 Career Development Award in CLinical Oncology, WUSM Clinical Research Training Center (2019-2021)
Abstract Achievement Award, American Society of Hematology (2019)
Outstanding Citizenship Award, WUSM Clinical Research Training Center (2021)
EvansMDS Young Investigator Award, Edward P. Evans Foundation (2021-2024)
K08 Mentored Clinical Scientist Research Career Development Award, NIH/NHLBI (2021-2026)

Affiliations

American Association for the Advancement of Science (AAAS)
American Physician Scientists Association (APSA)
Academy of Clinical Laboratory Physicians and Scientists (ACLPS)
Association for Molecular Pathology (AMP)
American Society of Hematology (ASH)
International Society for Experimental Hematology (ISEH)

Pathology (SOM)

CU Anschutz

Academic Office One

12631 East 17th Avenue

2nd Floor

Aurora, CO 80045

303-724-3704

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