Paula Welander received her undergraduate degree at Occidental College in Los Angeles. She pursued her PhD studies at the University of Illinois at Urbana-Champaign studying methanogenesis with Bill Metcalf. She was a postdoc with Dianne Newman and Roger Summons at MIT studying hopanoid and sterol function in bacterial species. She joined the Stanford faculty in 2013.

Academic Appointments

Administrative Appointments

  • NASA Astrobiology Postdoctoral Fellow, Massachusetts Institute of Technology (2012 - 2012)
  • Research Scientist, Massachusetts Institute of Technology (2011 - 2012)
  • NSF Minority Postdoctoral Fellow, Massachusetts Institute of Technology (2008 - 2011)
  • National Science Foundation Graduate Research Fellow, University of Illinois at Urbana-Champaign (2002 - 2005)
  • Graduate College Fellow, University of Illinois at Urbana-Champaign (2001 - 2007)
  • Research Associate I, Beckman Research Institute, City of Hope (1999 - 2001)
  • Research Assistant I, California Institute of Technology (1998 - 1999)

Honors & Awards

  • Terman Fellow, Stanford University (2014)
  • Gabilan Faculty Fellow, Stanford University (2013)
  • NASA Astrobiology Postdoctoral Fellowship, NASA Postdoctoral Program (2012)
  • OGD 2010 Best Paper Award, Geochemical Society (2011)
  • NSF Minority Postdoctoral Research Fellowship, National Science Foundation (2008)
  • Mame Shiao Debbie Award, University of Illinois at Urbana-Champaign (2006)
  • Outstanding Teaching Assistant, University of Illinois at Urbana-Champaign (2005-2006)
  • Recipient, Gordon Conference Minority Student Travel Grant (2003)
  • NSF Graduate Research Fellowship, National Science Foundation (2002)
  • Graduate College Fellowship, University of Illinois at Urbana-Champaign (2001)
  • Recipient, Declined, NIH MCB Training Grant Fellowship, University of Illinois at Urbana-Champaign (2001)
  • Recipient, Howard Hughes Medical Institute Undergraduate Research Grant (1998)
  • Fellow, Richter Fellowship (1997)
  • Undergraduate Research Academic Support Program Grant, Occidental College (1997)
  • Recipient, Cal Grant (1995 – 1998)

Boards, Advisory Committees, Professional Organizations

  • Editorial Board Member, Geobiology Journal (2014 - Present)
  • Member, American Geological Union (2013 - Present)
  • Member, American Society of Microbiology (2002 - Present)

Professional Education

  • Ph.D., University of Illinois at Urbana-Champaign, Urbana, IL, Microbiology (2007)
  • M.S., University of Illinois at Urbana-Champaign, Urbana, IL, Microbiology (2003)
  • B.A., Occidental College, Los Angeles, CA, Kinesiology (1998)

Current Research and Scholarly Interests

I am a microbiologist with interests in understanding the biosynthesis and physiological function of “molecular fossils” or biomarkers in extant bacteria. Biomarker signatures in ancient rocks have been used to reconstruct important events in the Earth’s past, such as the first appearance of major groups of organisms, the catastrophic loss of biodiversity and the evolution of cyanobacteria and oxygenic photosynthesis. Despite the significant implications biomarker studies have on our interpretation of microbial evolution and of the Earth’s ancient environment, our understanding of the phylogenetic distribution and physiological function of most of these molecules in modern bacteria is quite limited. My research utilizes a combination of bioinformatics, microbial genetics, physiology, and biochemistry to address three general questions that can be applied to any biomarker: 1) what is its phylogenetic distribution in modern bacteria? 2) what are its physiological roles in modern bacteria? 3) what is the evolutionary history of its biosynthetic pathway?

My teaching will focus on two of my main interests: 1) microbial physiology and metabolism and 2) how molecular biosignatures are used to study microbial systems in both modern and ancient environments.

2016-17 Courses

Stanford Advisees

Graduate and Fellowship Programs

  • Biology (School of Humanities and Sciences) (Phd Program)

All Publications

  • Synthesis of arborane triterpenols by a bacterial oxidosqualene cyclase. Proceedings of the National Academy of Sciences of the United States of America Banta, A. B., Wei, J. H., Gill, C. C., Giner, J. L., Welander, P. V. 2017; 114 (2): 245–50


    Cyclic triterpenoids are a broad class of polycyclic lipids produced by bacteria and eukaryotes. They are biologically relevant for their roles in cellular physiology, including membrane structure and function, and biochemically relevant for their exquisite enzymatic cyclization mechanism. Cyclic triterpenoids are also geobiologically significant as they are readily preserved in sediments and are used as biomarkers for ancient life throughout Earth's history. Isoarborinol is one such triterpenoid whose only known biological sources are certain angiosperms and whose diagenetic derivatives (arboranes) are often used as indicators of terrestrial input into aquatic environments. However, the occurrence of arborane biomarkers in Permian and Triassic sediments, which predates the accepted origin of angiosperms, suggests that microbial sources of these lipids may also exist. In this study, we identify two isoarborinol-like lipids, eudoraenol and adriaticol, produced by the aerobic marine heterotrophic bacterium Eudoraea adriatica Phylogenetic analysis demonstrates that the E. adriatica eudoraenol synthase is an oxidosqualene cyclase homologous to bacterial lanosterol synthases and distinct from plant triterpenoid synthases. Using an Escherichia coli heterologous sterol expression system, we demonstrate that substitution of four amino acid residues in a bacterial lanosterol synthase enabled synthesis of pentacyclic arborinols in addition to tetracyclic sterols. This variant provides valuable mechanistic insight into triterpenoid synthesis and reveals diagnostic amino acid residues to differentiate between sterol and arborinol synthases in genomic and metagenomic datasets. Our data suggest that there may be additional bacterial arborinol producers in marine and freshwater environments that could expand our understanding of these geologically informative lipids.

    View details for DOI 10.1073/pnas.1617231114

    View details for PubMedID 28028245

  • Fractionation of the methane isotopologues (CH4)-C-13, (CH3D)-C-12, and (CH3D)-C-13 during aerobic oxidation of methane by Methylococcus capsulatus (Bath) GEOCHIMICA ET COSMOCHIMICA ACTA Wang, D. T., Welander, P. V., Ono, S. 2016; 192: 186-202
  • Sterol Synthesis in Diverse Bacteria FRONTIERS IN MICROBIOLOGY Wei, J. H., Yin, X., Welander, P. V. 2016; 7


    Sterols are essential components of eukaryotic cells whose biosynthesis and function has been studied extensively. Sterols are also recognized as the diagenetic precursors of steranes preserved in sedimentary rocks where they can function as geological proxies for eukaryotic organisms and/or aerobic metabolisms and environments. However, production of these lipids is not restricted to the eukaryotic domain as a few bacterial species also synthesize sterols. Phylogenomic studies have identified genes encoding homologs of sterol biosynthesis proteins in the genomes of several additional species, indicating that sterol production may be more widespread in the bacterial domain than previously thought. Although the occurrence of sterol synthesis genes in a genome indicates the potential for sterol production, it provides neither conclusive evidence of sterol synthesis nor information about the composition and abundance of basic and modified sterols that are actually being produced. Here, we coupled bioinformatics with lipid analyses to investigate the scope of bacterial sterol production. We identified oxidosqualene cyclase (Osc), which catalyzes the initial cyclization of oxidosqualene to the basic sterol structure, in 34 bacterial genomes from five phyla (Bacteroidetes, Cyanobacteria, Planctomycetes, Proteobacteria, and Verrucomicrobia) and in 176 metagenomes. Our data indicate that bacterial sterol synthesis likely occurs in diverse organisms and environments and also provides evidence that there are as yet uncultured groups of bacterial sterol producers. Phylogenetic analysis of bacterial and eukaryotic Osc sequences confirmed a complex evolutionary history of sterol synthesis in this domain. Finally, we characterized the lipids produced by Osc-containing bacteria and found that we could generally predict the ability to synthesize sterols. However, predicting the final modified sterol based on our current knowledge of sterol synthesis was difficult. Some bacteria produced demethylated and saturated sterol products even though they lacked homologs of the eukaryotic proteins required for these modifications emphasizing that several aspects of bacterial sterol synthesis are still completely unknown.

    View details for DOI 10.3389/fmicb.2016.00990

    View details for Web of Science ID 000378390400001

    View details for PubMedID 27446030

  • Fractionation of the methane isotopologues 13CH4, 12CH3D, and 13CH3D during aerobic oxidation of methane by Methylococcus capsulatus (Bath) Geochimica et Cosmochimica Acta Wang, D. T., Welander, P. V., Ono, S. 2016; 192: 186-202
  • A distinct pathway for tetrahymanol synthesis in bacteria PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Banta, A. B., Wei, J. H., Welander, P. V. 2015; 112 (44): 13478-13483


    Tetrahymanol is a polycyclic triterpenoid lipid first discovered in the ciliate Tetrahymena pyriformis whose potential diagenetic product, gammacerane, is often used as a biomarker for water column stratification in ancient ecosystems. Bacteria are also a potential source of tetrahymanol, but neither the distribution of this lipid in extant bacteria nor the significance of bacterial tetrahymanol synthesis for interpreting gammacerane biosignatures is known. Here we couple comparative genomics with genetic and lipid analyses to link a protein of unknown function to tetrahymanol synthesis in bacteria. This tetrahymanol synthase (Ths) is found in a variety of bacterial genomes, including aerobic methanotrophs, nitrite-oxidizers, and sulfate-reducers, and in a subset of aquatic and terrestrial metagenomes. Thus, the potential to produce tetrahymanol is more widespread in the bacterial domain than previously thought. However, Ths is not encoded in any eukaryotic genomes, nor is it homologous to eukaryotic squalene-tetrahymanol cyclase, which catalyzes the cyclization of squalene directly to tetrahymanol. Rather, heterologous expression studies suggest that bacteria couple the cyclization of squalene to a hopene molecule by squalene-hopene cyclase with a subsequent Ths-dependent ring expansion to form tetrahymanol. Thus, bacteria and eukaryotes have evolved distinct biochemical mechanisms for producing tetrahymanol.

    View details for DOI 10.1073/pnas.1511482112

    View details for Web of Science ID 000364164900041

  • Methane Oxidation and Molecular Characterization of Methanotrophs from a Former Mercury Mine Impoundment. Microorganisms Baesman, S. M., Miller, L. G., Wei, J. H., Cho, Y., Matys, E. D., Summons, R. E., Welander, P. V., Oremland, R. S. 2015; 3 (2): 290-309


    The Herman Pit, once a mercury mine, is an impoundment located in an active geothermal area. Its acidic waters are permeated by hundreds of gas seeps. One seep was sampled and found to be composed of mostly CO₂ with some CH₄ present. The δ(13)CH₄ value suggested a complex origin for the methane: i.e., a thermogenic component plus a biological methanogenic portion. The relatively (12)C-enriched CO₂ suggested a reworking of the ebullitive methane by methanotrophic bacteria. Therefore, we tested bottom sediments for their ability to consume methane by conducting aerobic incubations of slurried materials. Methane was removed from the headspace of live slurries, and subsequent additions of methane resulted in faster removal rates. This activity could be transferred to an artificial, acidic medium, indicating the presence of acidophilic or acid-tolerant methanotrophs, the latter reinforced by the observation of maximum activity at pH = 4.5 with incubated slurries. A successful extraction of sterol and hopanoid lipids characteristic of methanotrophs was achieved, and their abundances greatly increased with increased sediment methane consumption. DNA extracted from methane-oxidizing enrichment cultures was amplified and sequenced for pmoA genes that aligned with methanotrophic members of the Gammaproteobacteria. An enrichment culture was established that grew in an acidic (pH 4.5) medium via methane oxidation.

    View details for DOI 10.3390/microorganisms3020290

    View details for PubMedID 27682090

  • Elucidation of the Burkholderia cenocepacia hopanoid biosynthesis pathway uncovers functions for conserved proteins in hopanoid-producing bacteria ENVIRONMENTAL MICROBIOLOGY Schmerk, C. L., Welander, P. V., Hamad, M. A., Bain, K. L., Bernards, M. A., Summons, R. E., Valvano, M. A. 2015; 17 (3): 735-750


    Hopanoids are bacterial surrogates of eukaryotic membrane sterols and among earth's most abundant natural products. Their molecular fossils remain in sediments spanning more than a billion years. However, hopanoid metabolism and function are not fully understood. Burkholderia species are environmental opportunistic pathogens that produce hopanoids and also occupy diverse ecological niches. We investigated hopanoids biosynthesis in Burkholderia cenocepacia by deletion mutagenesis and structural characterization of the hopanoids produced by the mutants. The enzymes encoded by hpnH and hpnG were essential for production of all C35 extended hopanoids, including bacteriohopanetetrol (BHT), BHT glucosamine and BHT cyclitol ether. Deletion of hpnI resulted in BHT production, while ΔhpnJ produced only BHT glucosamine. Thus, HpnI is required for BHT glucosamine production while HpnJ is responsible for its conversion to the cyclitol ether. The ΔhpnH and ΔhpnG mutants could not grow under any stress condition tested, whereas ΔhpnI, ΔhpnJ and ΔhpnK displayed wild-type growth rates when exposed to detergent, but varying levels of sensitivity to low pH and polymyxin B. This study not only elucidates the biosynthetic pathway of hopanoids in B. cenocepacia, but also uncovers a biosynthetic role for the conserved proteins HpnI, HpnJ and HpnK in other hopanoid-producing bacteria.

    View details for DOI 10.1111/1462-2920.12509

    View details for Web of Science ID 000351435600019

    View details for PubMedID 24888970

  • Methane Oxidation and Molecular Characterization of Methanotrophs from a Former Mercury Mine Impoundment. Microorganisms Microorganisms Baesman, S. M., Miller, L. G., Wei, J. H., Cho, Y., Matys, E. D., Summons, R. E., Welander, P. V., Oremland, R. E. 2015; 3 (2): 290-309
  • Diverse capacity for 2-methylhopanoid production correlates with a specific ecological niche ISME JOURNAL Ricci, J. N., Coleman, M. L., Welander, P. V., Sessions, A. L., Summons, R. E., Spear, J. R., Newman, D. K. 2014; 8 (3): 675-684


    Molecular fossils of 2-methylhopanoids are prominent biomarkers in modern and ancient sediments that have been used as proxies for cyanobacteria and their main metabolism, oxygenic photosynthesis. However, substantial culture and genomic-based evidence now indicates that organisms other than cyanobacteria can make 2-methylhopanoids. Because few data directly address which organisms produce 2-methylhopanoids in the environment, we used metagenomic and clone library methods to determine the environmental diversity of hpnP, the gene encoding the C-2 hopanoid methylase. Here we show that hpnP copies from alphaproteobacteria and as yet uncultured organisms are found in diverse modern environments, including some modern habitats representative of those preserved in the rock record. In contrast, cyanobacterial hpnP genes are rarer and tend to be localized to specific habitats. To move beyond understanding the taxonomic distribution of environmental 2-methylhopanoid producers, we asked whether hpnP presence might track with particular variables. We found hpnP to be significantly correlated with organisms, metabolisms and environments known to support plant-microbe interactions (P-value<10(-6)); in addition, we observed diverse hpnP types in closely packed microbial communities from other environments, including stromatolites, hot springs and hypersaline microbial mats. The common features of these niches indicate that 2-methylhopanoids are enriched in sessile microbial communities inhabiting environments low in oxygen and fixed nitrogen with high osmolarity. Our results support the earlier conclusion that 2-methylhopanoids are not reliable biomarkers for cyanobacteria or any other taxonomic group, and raise the new hypothesis that, instead, they are indicators of a specific environmental niche.

    View details for DOI 10.1038/ismej.2013.191

    View details for Web of Science ID 000331879900016

    View details for PubMedID 24152713

  • Molecular indicators of microbial diversity in oolitic sands of Highborn Cay, Bahamas Geobiology Edgecomb, V. P., Bernhard, J. M., Beaudoin, D., Pruss, S., Welander, P. V., Shubotz, F., Mehay, S., Gillespie, A. L., Summons, R. E. 2013; 11: 234-251
  • Identification and quantification of polyfunctionalized hopanoids by high temperature gas chromatography-mass spectrometry Organic Geochemistry Sessions, A. L., Zhang, L., Welander, P. V., Doughty, D. M., Summons, R. E., Newman, D. K. 2013; 56: 120-130
  • Identification and characterization of Rhodopseudomonas palustris hopanoid biosynthesis mutants Geobiology Welander, P. V., Doughty, D. M., Wu, C. H., Mehay, S., Summons, R. E., Newman, D. K. 2012; 10: 163-177
  • Identification of the bacteriochlorophylls, carotenoids, quinones, lipids, and hopanoids of Candidatus Chloracidobacterium thermophilum Journal of Bacteriology Garcia Costas, A. M., Tsukatani, Y., Rijpstra, W. I., Schouten, S., Welander, P. V., Summons, R. E., Bryant, D. A. 2012; 194: 1158-68
  • Discovery, taxonomic distribution, and phenotypic characterization of a gene required for 3-methylhopanoid production Proceedings of the National Academy of Sciences Welander, P. V., Summons, R. E. 2012; 109: 12905-12910
  • Using Taguchi-based statistics to produce robust PCR results Bioprocessing Welander, P., Cantin, E., Lundberg, P. 2011; 10: 22-26
  • Identification of a methylase required for 2-methylhopanoid production and implications for the interpretation of sedimentary hopanes Proceedings of the National Academy of Sciences Welander , P. V., Coleman, M. C., Sessions, A. L., Summons, R. E., Newman, D. K. 2010; 107: 8537-8542
  • Hopanoids play a role in membrane integrity and pH homeostasis in Rhodopseudomonas palustris TIE-1 Journal of Bacteriology Welander, P. V., Hunter, R. C., Zhang, L., Sessions, A. L., Summons, R. E., Newman, D. K. 2009; 191: 6145-6156
  • The continuing puzzle of the great oxidation event Current Biology Sessions, A. L., Doughty, D. M., Welander, P. V., Summons, R. E., Newman, D. K. 2009; 19: R567-R574
  • Mutagenesis of the C1 oxidation pathway in Methanosarcina barkeri: new insights into the Mtr/Mer bypass pathway Journal of Bacteriology Welander, P. V., Metcalf, W. W. 2008; 190: 1928-1936
  • Tumor necrosis factor (TNF) protects resistant C57BL/6 mice against herpes simplex virus-induced encephalitis independently of signaling via TNF receptor 1 or 2 Journal of Virology Lundberg, P., Welander, P. V., Edwards, 3rd, C. K., van Rooijen, N., Cantin, E. 2007; 81: 1451-1460
  • Loss of the mtr operon in Methanosarcina blocks growth on methanol, but not methanogenesis, and reveals an unknown methanogenic pathway Proceedings of the National Academy of Sciences Welander, P. V., Metcalf, W. W. 2005; 102: 10664-10669
  • Herpes simplex virus type 1 DNA is immunostimulatory in vitro and in vivo Journal of Virology Lundberg, P., Welander, P., Han, X., Cantin, E. 2003; 77: 11158-11169
  • A locus on mouse chromosome 6 that determines resistance to herpes simplex virus also influences reactivation, while an unlinked locus augments resistance of female mice Journal of Virology Lundberg, P., Welander, P., Openshaw, H., Nalbandian, C., Edwards, C., Moldawer, L., Cantin, E. 2003; 77: 11661-11673