Anders M. Näär is a Professor of Metabolic Biology in the Department of Nutritional Sciences & Toxicology at the University of California, Berkeley. He received a B.S. degree in biochemistry/biotechnology from the University of Lund, Sweden, in 1988, and a Ph.D. in Molecular Pathology with M. Geoff Rosenfeld at UC San Diego/HHMI in 1995, studying nuclear hormone receptor mechanisms of gene regulation. He was a postdoctoral research fellow with Robert Tjian at UC Berkeley/HHMI, where he discovered the human Mediator transcriptional co-activator complex. Dr. Näär was a Professor in the Department of Cell Biology, Harvard Medical School and the Massachusetts General Hospital Cancer Center, from 2001-2018.

The primary focus of the Näär lab is to elucidate transcriptional and microRNA regulatory mechanisms governing cholesterol/lipid and metabolic homeostasis. Our studies over the last 20 years of the sterol- regulatory element-binding protein (SREBP) family of transcription factors, master regulators of cholesterol/lipid synthesis and trafficking, have led to an atomic-level understanding of the molecular mechanism of SREBP gene regulation. We have parlayed this detailed mechanistic knowledge to guide small molecule therapeutic targeting efforts resulting in the development of nanomolar inhibitors of the interaction of SREBPs with transcriptional co-activators. Ongoing NMR structure-guided medicinal chemistry efforts are aimed at further improving on these inhibitors, with the goal of identifying effective therapeutic modalities as treatments for diseases linked to abnormal cholesterol/lipids and metabolism, including many types of cancers, as well as metabolic syndrome, type 2 diabetes, and cardiovascular disease. Our work is innovative as it challenges the prevalent dogma that protein-protein interactions are not druggable.

Our studies have also identified microRNAs as crucial regulators of cholesterol/lipids and metabolism. We uncovered miR-33a/b as intronic microRNAs present in the SREBP genes that act in concert with the host genes to govern cholesterol/lipid homeostasis. Based on potent effects of antisense oligonucleotides (ASOs) targeting miR-33a/b on atherosclerosis in rodent models, we are currently pursuing state-of-the art locked nucleic acid (LNA) ASO technologies as novel and safe treatments for familial hypercholesterolemia and other cardiovascular diseases, as well as age-related macular degeneration (AMD).

Employing genome-wide association study data from >188,000 individuals we have identified a microRNA, miR-128-1, as a crucial regulator of circulating cholesterol and triglycerides. Surprisingly, miR-128- 1 is located in a genomic region on human chromosome 2 that is also strongly linked to recent positive selection, type 2 diabetes, and obesity. Based on our supportive in vivo data in several mouse obesity and metabolic disease models, we hypothesize that miR-128-1 represents a thrifty microRNA that acts as a potent negative regulator of energy expenditure, selected as a human evolutionary adaptation to promote fat storage to survive famine in ancient times. Currently, this represents a maladaptation in the developed world with abundant food, resulting in increased risk for cardio-metabolic diseases such as coronary artery disease, Metabolic Syndrome (MetS), obesity, type 2 diabetes, and non-alcoholic fatty liver diseases (NAFLD/NASH). Indeed, our ongoing and planned studies are aimed at developing LNA ASO modalities targeting miR-128-1 for the treatment of these metabolic diseases, and unpublished results from mouse obesity and NASH models look very promising. We have also unexpectedly found a link of miR-128-1 to Duchenne Muscular Dystrophy (DMD), a rare and early lethal muscle wasting disorder, and we are investigating a potential pathological disease modifying role of miR-128-1 in DMD, and whether it might represent a target for LNA ASOs as a novel DMD treatment in conjunction with other approaches such as exon-skipping ASO modalities.

As discussed above, antisense oligonucleotides hold great promise in therapeutic targeting of pathological RNAs. We have applied our deep expertise with LNA ASO technologies to target RNA viruses of great societal concern, including Ebola and SARS-CoV-2. We have developed potent (nM) LNA ASOs targeting Ebola viral RNAs encoding key functional proteins and the host receptor NPC1, which effectively prevented replication of a pseudovirus harboring the Ebola GP in infected human cells. When the current Covid-19 pandemic began in earnest in the U.S., my lab pivoted to designing and testing LNA ASOs targeting the SARS-CoV-2 viral RNA, as well as the ACE2 host cell receptor. We were successful in obtaining potent (pM to low nM IC50 in human cells) LNA ASOs directed against the virus and ACE2, and focused on one LNA ASO that exhibited exceptional activity in blocking viral replication in human cells. This LNA ASO, which targets the SL1 stem-loop structure in the 5’ leader sequence of the virus, was found to prevent SARS-CoV-2 viral replication in the K18-hACE2 mouse model when introduced intranasally, without formulation or delivery agents. Indeed, once daily intranasal administration of the LNA ASO in saline effectively (~98-99%) blocked lung infection of all variants of concern tested, including alpha, beta, delta, and omicron variants. These studies provide strong support for the feasibility of using ASOs to target SARS-CoV-2 and other RNA viruses of pandemic potential.

We have also developed an in silico drug screening approach capable of screening ultra-large small molecule libraries (1.4B compounds) in about a week using Google Cloud or AWS and applied this technology to targeting all known structures of SARS-CoV-2. With this approach, we screened 40 targets with 50 billion docking instances, and found potent (nM binding affinity by SPR) hits for all targets, with efficacious compounds (as good as remdesivir, our positive control, for every target) lowering SARS-CoV-2 viral replication in VeroE6 cells with low μM IC50. 

Altogether, we are taking advantage of deep insights into molecular underpinnings of common and rare human diseases gained from our mechanistic studies to develop novel therapeutic targeting strategies.

Professor and Vice-chair, Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA (2018 – present)

Biologist, Department of Medicine, Massachusetts General Hospital (2013-2018)

Professor of Cell Biology, Harvard Medical School (2012-2018)

Associate Professor of Cell Biology, Harvard Medical School (2009-2012)

Member, Dana Farber/Harvard Cancer Center (2002-2018)

Principal Investigator, Massachusetts General Hospital Cancer Center (2001-2018)

Assistant Cell Biologist, Department of Medicine, Massachusetts General Hospital (2001-2012)

Assistant Professor of Cell Biology, Harvard Medical School (2001-2009)

Postdoctoral Fellow at University of California, Berkeley (1995 – 2001) in Biochemistry (Advisor: Dr. Robert Tjian)

Ph.D. University of California, San Diego (1995) in Molecular Pathology (Advisor: Dr. Michael G. Rosenfeld)

B.S. University of Lund, Sweden (1988) in Biochemistry/Biotech

California Fellowship. Education Abroad Program. University of Lund, Sweden and University of California, San Diego (1988-1990)
Paulsen Foundation Award, UC San Diego (1992)
Sweden-America Foundation Fellowship (1992-1993)
Damon Runyon-Walter Winchell Cancer Foundation Postdoctoral Fellowship Award (1995-1998)
Recipient of the 2003 Dennis and Marsha Dammerman Scholar Award of the Damon Runyon Cancer Research Foundation (2002-2005)
Massachusetts General Hospital Research Scholar Award (2012-2017)
Massachusetts General Hospital Research Scholar Award (2017-2019)