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Discoveries in Z-DNA Biology, RNA Editing and the Encoding of Genetic Information by Flipons. Advances in Immunology based on Contextual Cell Death and the Regulation of Anti-Tumor Responses by Complement-mediated control of Immune Synapse Formation.At InsideOutBio, my focus as founder and head of discovery is on translating the power of human genetics to therapeutics. We have developed a novel therapeutic for the induction of anti-tumor responses. Our approach exploits the genetics of the complement system. and pioneers the targeting of the Complement C3 Checkpoint. We have been able to quickly move from concept to proof of mechanism and produce tumor regression in our preclinical models. All of this was done at low cost with the goal of moving safely to the clinic as fast as we can. InsideOutBio has also contributed to our understanding of the role of RNA editing in cancer. Data gathered by many investigators examining families with certain Mendelian diseases provided evidence for a role of the left-handed Z-DNA conformation in regulating interferon responses essential to anti-tumor immunity. The work supports the targeting of Z-DNA binding proteins and RNA editing as a new therapeutic approach to treating cancer. While cancer biology traditionally focuses on mutations to codons, our interest is on the role of flipons in tumor biology. Flipons consist of sequences that encode alternative DNA conformations like Z-DNA. They allow the compilation of different RNA transcripts from the same DNA sequence. Besides cancer, they play a role in many other diseases.
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FounderInsideoutbio 2017 - PresentCharlestown, Ma, Us
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FounderInsideoutbio Jan 2017 - 2017Charlestown, Ma, UsA Stealth Immuno-Oncology Company Developing a Novel Platform for Engineered Therapeutics. The IP is wholly owned by InsideOutBio.
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Associate Principal Scientist Human Genetics And PharmacogeneticsMerck May 2014 - Dec 2016Rahway, New Jersey, UsWhile at Merck Research Laboratories, I developed a novel Bioinformatic Algorithm to analyze the Moffat Cancer Center Collection of 10,000 Tumor-Derived MicroArrays that lead to the initiation of a novel Checkpoint Inhibitor Program. Another company, Calithera, recently published validation of the target IL4I1 in synergy with a checkpoint inhibitor using a pre-clinical melanoma model. Other work in target identification and validation in immunology and immuno-oncology was also performed at Merck in support of other programs that are still ongoing.1. St Pierre C, Guo J, Shin JD, Engstrom LW, Lee HH, Herbert A, Surdi L, Baker J, Salmon M, Shah S, Ellis JM, Houshyar H, Crackower MA, Kleinschek MA, Jones DC, Hicks A, Zaller DM, Alves SE, Ramadas RA. A human tissue-based functional assay platform to evaluate the immune function impact of small molecule inhibitors that target the immune system. PLoS One. 2017;12(7):e0180870. Epub 2017/07/19. doi: 10.1371/journal.pone.0180870. PubMed PMID: 28719615; PMCID: PMC5515432. -
Associate ProfessorBoston University Aug 2000 - May 2014Boston, Ma, UsThe work I initiated at Boston University was the first Genome Wide Association Study (GWAS) in a human population based on data collected by the Framingham Heart Study. New methods based on the family structure provided a solution to the multiple testing problem arising from the use of hundreds of polymorphic markers in this approach. This work provided initial validation of the GWAS approach.1. Herbert A. The fat tail of obesity as told by the genome. Curr Opin Clin Nutr Metab Care. 2008;11(4):366-70. Epub 2008/06/11. doi: 10.1097/MCO.0b013e3283034990. PubMed PMID: 18541993; PMCID: PMC2770374.2. Herbert A, Lenburg ME, Ulrich D, Gerry NP, Schlauch K, Christman MF. Open-access database of candidate associations from a genome-wide SNP scan of the Framingham Heart Study. Nat Genet. 2007;39(2):135-6. Epub 2007/01/31. doi: 10.1038/ng0207-135. PubMed PMID: 17262019.3. Herbert A, Gerry NP, McQueen MB, Heid IM, Pfeufer A, Illig T, Wichmann HE, Meitinger T, Hunter D, Hu FB, Colditz G, Hinney A, Hebebrand J, Koberwitz K, Zhu X, Cooper R, Ardlie K, Lyon H, Hirschhorn JN, Laird NM, Lenburg ME, Lange C, Christman MF. A common genetic variant is associated with adult and childhood obesity. Science. 2006;312(5771):279-83. Epub 2006/04/15. doi: 10.1126/science.1124779. PubMed PMID: 16614226. -
ConsultantCoriell Institute For Medical Research Jun 2007 - Feb 2013Camden, New Jersey, UsCoriell Personalized Medicine CollaborativePersonalized medicine> Provided consultative guidance and advice to the Coriell Personalized Medicine Collaborative and Operation Smile in the areas of personalized medicine; drafted IRB protocols for the successful launch of the study.> Provided consultative guidance to Operation Smile to establish protocols for the Operation Smile International Family Study to understand the causes of Cleft Lip and Palate, adapting high tech approaches to the low tech environment found in many of the countries Operation Smile operates in. -
Research ScientistMit Aug 1988 - Aug 2000Cambridge, Ma, UsMy work on Z-DNA lead to the identification of the RNA editing enzyme as the first high affinity binding protein for the left-handed conformation. Mapping of mutations to the Z-DNA binding domain to diseases using Mendelian Genetics established a role for Z-DNA in biology and support for the flipon concept describing the encoding of genetic information in DNA structure rather than just sequence. The role of ADAR based on the Z-DNA dependent regulation of type I interferon responses has opened up a new paradigm for cancer treatment, orthogonal to those based on codon mutations. This work has advanced our basic understanding of the different ways DNA encodes genetic information and to the clinical application of this new biology.1. Herbert A. Mendelian disease caused by variants affecting recognition of Z-DNA and Z-RNA by the Zalpha domain of the double-stranded RNA editing enzyme ADAR. Eur J Hum Genet. 2020;28(1):114-7. Epub 2019/07/20. doi: 10.1038/s41431-019-0458-6. PubMed PMID: 31320745; PMCID: PMC6906422.2. Herbert A. Z-DNA and Z-RNA in human disease. Commun Biol. 2019;2:7. Epub 2019/02/08. doi: 10.1038/s42003-018-0237-x. PubMed PMID: 30729177; PMCID: PMC6323056.3. Herbert A. ADAR and Immune Silencing in Cancer. Trends Cancer. 2019;5(5):272-82. Epub 2019/06/09. doi: 10.1016/j.trecan.2019.03.004. PubMed PMID: 31174840.4. Herbert A. A Genetic Instruction Code Based on DNA Conformation. Trends Genet. 2019;35(12):887-90. 5. Herbert A, Rich A. The role of binding domains for dsRNA and Z-DNA in the in vivo editing of minimal substrates by ADAR1. Proc Natl Acad Sci U S A. 2001;98(21):12132-7.6. Herbert A, Alfken J, Kim YG, Mian IS, Nishikura K, Rich A. A Z-DNA binding domain present in the human editing enzyme, double-stranded RNA adenosine deaminase. Proc Natl Acad Sci U S A. 1997;94(16):8421-67. Herbert AG, Rich A. A method to identify and characterize Z-DNA binding proteins using a linear oligodeoxynucleotide. Nucleic Acids Res. 1993;21(11):2669-72
Alan Herbert Skills
Alan Herbert Education Details
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The University Of AucklandImmunobiology -
The University Of AucklandBachelor Of Surgery (Mb.Chb) (Md Equivalent)
Frequently Asked Questions about Alan Herbert
What company does Alan Herbert work for?
Alan Herbert works for Insideoutbio
What is Alan Herbert's role at the current company?
Alan Herbert's current role is Therapeutics for Turning Cold Tumors Hot. Designs powered by Human Genetics!.
What is Alan Herbert's email address?
Alan Herbert's email address is al****@****bio.com
What is Alan Herbert's direct phone number?
Alan Herbert's direct phone number is +185696*****
What schools did Alan Herbert attend?
Alan Herbert attended The University Of Auckland, The University Of Auckland.
What are some of Alan Herbert's interests?
Alan Herbert has interest in Sailing, Children, Skiing.
What skills is Alan Herbert known for?
Alan Herbert has skills like Drug Discovery, Genetics And Genomics, Bioinformatics, Human Immunology, Tumor Immunology, Population Genetics, Statistical Genetics, Protein Chemistry, Biochemistry, Metabolic Switches, Molecular Biology, Rna Biology.
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